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Hypoglycaemia is reduced with use of inhaled Technosphere® Insulin relative to insulin aspart in type 1 diabetes mellitus.
Seaquist, ER, Blonde, L, McGill, JB, Heller, SR, Kendall, DM, Bumpass, JB, Pompilio, FM, Grant, ML
Diabetic medicine : a journal of the British Diabetic Association. 2020;(5):752-759
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Abstract
AIM: To evaluate the effect of final HbA1c levels on the incidences of hypoglycaemia in participants with type 1 diabetes treated with inhaled Technosphere® Insulin or subcutaneous insulin aspart, reported in alignment with the International Hypoglycaemia Study Group recommendations. METHODS In the randomized, phase 3, multicentre AFFINITY-1 study, adults (N = 375) who had type 1 diabetes for ≥ 12 months and an HbA1c level of 58-86 mmol/mol (7.5-10.0%) were randomized to receive basal insulin plus either inhaled Technosphere Insulin or subcutaneous insulin aspart. This was a post-hoc regression analysis on a subset (N = 279) of the randomized AFFINITY-1 cohort for whom baseline and end-of-treatment HbA1c values were reported. Primary outcome measures were incidence and event rates for levels 1, 2 and 3 hypoglycaemia, respectively defined as blood glucose levels of ≤ 3.9 mmol/l, < 3.0 mmol/l or requiring external assistance for recovery. RESULTS Participants treated with Technosphere Insulin experienced statistically significantly fewer level 1 and 2 hypoglycaemic events and a lower incidence of level 3 hypoglycaemia than participants treated with insulin aspart. The lower rate of hypoglycaemia with Technosphere Insulin was observed across the range of end-of-treatment HbA1c levels. Technosphere Insulin was associated with higher rates of hypoglycaemia 30-60 min after meals, but significantly lower rates 2-6 h after meals. CONCLUSIONS Participants using Technosphere Insulin experienced clinically non-inferior glycaemic control and lower hypoglycaemia rates across a range of HbA1c levels compared with participants receiving insulin aspart. ClinicalTrials.gov: NCT01445951.
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Anthropometric outcomes in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective glycemic control from single center.
Calapkulu, M, Cander, S, Gul, OO, Ersoy, C
Diabetes & metabolic syndrome. 2019;(1):284-288
Abstract
INTRODUCTION Dapagliflozin is an antidiabetic drug that has been used as a member of the new antidiabetic drug group that acts by inhibiting SGLT-2 and increasing urinary glucose excretion. With numerous controlled experimental studies of dapagliflozin, evaluation of real-life data after entry into clinical practice is an important condition. In our study, the effects of dapagliflozin on glycemic control and anthropometric measurements were investigated retrospectively. METHODS A-total of thirty-one type 2 diabetics were enrolled in the study. Data of before dapagliflozin and three and six months of treatment were recorded. RESULTS Dapagliflozin reduced HbA1c levels by 0,9% at 3 months and 0,79% at 6 months. Fasting plasma glucose decreased 41,1 mg/dl in the 3rd and 42 mg/dl in the 6th, postprandiyal glucose decreased 86,3 mg/dl in the 3rd and 74,2 mg/dl in the 6th. In the 3rd and 6th, body weights decreased by 3,3 kg and 4,2 kg, BMI decreased by 1,3 kg/m2 and 1,6 kg/m2 respectively. Similarly, it was observed that the waist circumference decreased by 1,3 cm at the end of 6th. CONCLUSION Our data show that SGLT-2 inhibitors provide glycemic control with reduce HbA1c levels by 0.8-0.9%, and reduce fasting and postprandial plasma glucose levels without increasing the risk of hypoglycemia and causing weight lose around 5% at the six mounths. SGLT-2 inhibitors were found to be more effective in reduce postprandiyal plasma glucose in patients who did not use insulin and fasting plasma glucose in patients with diabetes mellitus less than 10 years.
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Use of flash glucose monitoring system in assessing safety of the SGLT2 inhibitors during Ramadan fasting in high risk insulin treated patients with type 2 diabetes.
Abdelgadir, E, Rashid, F, Bashier, A, Al Saeed, M, Khalifa, A, Alawadi, F, Hassanein, M
Diabetes & metabolic syndrome. 2019;(5):2927-2932
Abstract
BACKGROUND The risks of hypoglycemia, dehydration and kidney injury may theoretically be aggravated by people with type 2 diabetes treated with Insulin and SGLT2 inhibitors during Ramadan. Data on safety and efficacy of SGLT2-I in people with type 2 diabetes treated with insulin is scanty. We aimed to assess the impact of SGLT2 inhibitors during Ramadan in high-risk patients with type 2 diabetes treated with insulin, on hypoglycemia, glycemic control and kidney function. METHODS This is a prospective interventional study on high-risk diabetes patients who insisted on fasting. All patients were treated with insulin ± SGLT2I. All patients received a FGMS and Ramadan focused education. All patients attended clinic before and post Ramadan where they were advised on treatment modification as well as biometric and biochemical measurements. RESULTS 95 patients enrolled in the study and 49 of them were on SGLT2i. There was a no significant change in creatinine in both groups. FGMS showed an improvement in the sensor-calculated HbA1c from 7.3 ± 1.5 to 6.8 ± 1.1 and from 8 ± 1.6 to 7.7 ± 1.5 in the SGLT2 group and the non-SGT2i groups, respectively. The hypoglycemia was predominantly reported during Ramadan between 12:00 to 18:00 h, while in pre-Ramadan readings was during 2400-0600 and 1200-1800 slots. CONCLUSIONS This is the first study that assesses the use of SGLT2i along with insulin during Ramadan, using FGMS in high-risk patients with type 2 diabetes under optimal care. There was minimal interruption of fasting, significant improvement in glycemic control, and no significant change in the kidney function after Ramadan.
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Long-term safety of long-acting octreotide in patients with diabetic retinopathy: results of pooled data from 2 randomized, double-blind, placebo-controlled phase 3 studies.
Pivonello, R, Muscogiuri, G, Holder, G, Paul, M, Sarp, S, Lesogor, A, Jordaan, P, Eisinger, J, Colao, A
Endocrine. 2018;(1):65-72
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Abstract
PURPOSE Octreotide (OCT) has been successfully used for treatment of acromegaly and neuroendocrine tumors for more than 30 years. However, long-term safety of OCT has not been documented in placebo-controlled setting. This present analysis pooled safety data from two similarly-designed, randomized, and placebo-controlled studies to evaluate long-term safety of long-acting OCT (20, 30 mg); targeted post-hoc analyzes focused on cardiac, hepatic, and renal safety. METHODS Two studies (NCT00131144, NCT001308450) were conducted in patients with diabetic retinopathy (OCT20 = 191, OCT30 = 348, placebo = 347). In this analysis, patients were stratified based on baseline glomerular filtration rate. Hepatic, cardiac, and renal adverse events (AEs) were identified by standardized MedDRA queries. RESULTS Median duration of exposure was >3.5 years. Most common AEs reported with OCT were diarrhea, cholelithiasis, hypoglycemia, nasopharyngitis, and hypertension. Incidence of cardiac events (QT prolongation and arrhythmia) with OCT20 and OCT30 were comparable to placebo (OCT20, RR = 1.11 [95% CI, 0.61-2.03]; OCT30, RR = 1.09 [95% CI, 0.70-1.68]). For ECG findings, changes in QTcF were similar in treatment groups, and outliers did not exceed 480 ms. Incidence of cardiac ischemia was lower with OCT than placebo (OCT20 = 12.6%, OCT30 = 10.6%, placebo = 15.3%). Incidence of liver-related AEs was higher with OCT30 than placebo (RR = 2.04 [95% CI, 1.28-3.26]); incidences were comparable with OCT20 and placebo (RR = 1.50 [95% CI, 0.69-3.25]). Overall incidences of renal AEs were comparable between treatment groups (OCT20 = 5.8%; OCT30 = 6.3%; placebo = 7.2%). Drug-related SAEs were reported more frequently with OCT (OCT20 = 7.9%; OCT30 = 10.1%; placebo = 3.5%); predominantly gallbladder-related, GI-related, and hypoglycemia. CONCLUSIONS The results from these long-term placebo-controlled studies confirm the established safety profile of long-acting OCT, in particular low risk of cardiac, hepatic and renal toxicity in a high-risk population.
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Glucose Gel as a Potential Alternative Treatment to Infant Formula for Neonatal Hypoglycaemia in Australia.
Barber, RL, Ekin, AE, Sivakumar, P, Howard, K, O'Sullivan, TA
International journal of environmental research and public health. 2018;(5)
Abstract
Infant formula is often used as a treatment for neonatal hypoglycaemia in Australia; however, there are concerns that this may jeopardise mother-baby bonding and breastfeeding. Successful use of glucose gel as an alternative treatment for hypoglycaemia has been reported. We wanted to investigate in a pilot study whether the use of glucose gel has the potential to quickly and safely restore normoglycaemia in the infants of diabetic mothers in an Australian setting. Infants with asymptomatic hypoglycaemia were treated with glucose gel (n = 36) and compared to a historical group of infants which had been treated with infant formula (n = 24). Within 15 min of the first treatment, the gel group had a mean blood glucose level (BGL) of 2.6 mmol/L, and 2.7 mmol/L 30 min after the second treatment. This was lower than the BGL after the first treatment for the formula group, which rose to a mean of 2.8 then to 3.2 mmol/L after the second treatment (p = 0.003). In successfully treated infants, administration of the gel resulted in normoglycaemia within 30 min. The likelihood of special care nursery admission was not significantly different between the groups, although we had a small sample size, and our findings should be interpreted with caution. These pilot results provide support for further investigations into the use of glucose gel as an alternative treatment to infant formula.
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Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial.
Lablanche, S, Vantyghem, MC, Kessler, L, Wojtusciszyn, A, Borot, S, Thivolet, C, Girerd, S, Bosco, D, Bosson, JL, Colin, C, et al
The lancet. Diabetes & endocrinology. 2018;(7):527-537
Abstract
BACKGROUND Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. METHODS In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11 000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified β-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed. FINDINGS Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified β-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p<0·0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90·5 mL/min (IQR 76·6-94·0) to 71·8 mL/min (59·0-89·0) was observed in islet recipients who had not previously received a kidney graft and from 63·0 mL/min (55·0-71·0) to 57·0 mL/min (45·5-65·1) in islet recipients who had previously received a kidney graft. INTERPRETATION For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients. FUNDING Programme Hospitalier de Recherche Clinique grant from the French Government.
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Closed-Loop Insulin Delivery for Adults with Type 1 Diabetes Undertaking High-Intensity Interval Exercise Versus Moderate-Intensity Exercise: A Randomized, Crossover Study.
Jayawardene, DC, McAuley, SA, Horsburgh, JC, Gerche, A, Jenkins, AJ, Ward, GM, MacIsaac, RJ, Roberts, TJ, Grosman, B, Kurtz, N, et al
Diabetes technology & therapeutics. 2017;(6):340-348
Abstract
BACKGROUND We aimed to compare closed-loop glucose control for people with type 1 diabetes undertaking high-intensity interval exercise (HIIE) versus moderate-intensity exercise (MIE). METHODS Adults with type 1 diabetes established on insulin pumps undertook HIIE and MIE stages in random order during automated insulin delivery via a closed-loop system (Medtronic). Frequent venous sampling for glucose, lactate, ketones, insulin, catecholamines, cortisol, growth hormone, and glucagon levels was performed. The primary outcome was plasma glucose <4.0 mmol/L for ≥15 min, from exercise commencement to 120 min postexercise. Secondary outcomes included continuous glucose monitoring and biochemical parameters. RESULTS Twelve adults (age mean ± standard deviation 40 ± 13 years) were recruited; all completed the study. Plasma glucose of one participant fell to 3.4 mmol/L following MIE completion; no glucose levels were <4.0 mmol/L for HIIE (primary outcome). There were no glucose excursions >15.0 mmol/L for either stage. Mean (±standard error) plasma glucose did not differ between stages pre-exercise; was higher during exercise in HIIE than MIE (11.3 ± 0.5 mmol/L vs. 9.7 ± 0.6 mmol/L, respectively; P < 0.001); and remained higher until 60 min postexercise. There were no differences in circulating free insulin before, during, or postexercise. During HIIE compared with MIE, there were greater increases in lactate (P < 0.001), catecholamines (all P < 0.05), and cortisol (P < 0.001). Ketones increased more with HIIE than MIE postexercise (P = 0.031). CONCLUSIONS Preliminary findings suggest that closed-loop glucose control is safe for people undertaking HIIE and MIE. However, the management of the postexercise rise in ketones secondary to counter-regulatory hormone-induced insulin resistance observed with HIIE may represent a challenge for closed-loop systems.
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Outpatient Closed-Loop Control with Unannounced Moderate Exercise in Adolescents Using Zone Model Predictive Control.
Huyett, LM, Ly, TT, Forlenza, GP, Reuschel-DiVirgilio, S, Messer, LH, Wadwa, RP, Gondhalekar, R, Doyle, FJ, Pinsker, JE, Maahs, DM, et al
Diabetes technology & therapeutics. 2017;(6):331-339
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BACKGROUND The artificial pancreas (AP) has the potential to improve glycemic control in adolescents. This article presents the first evaluation in adolescents of the Zone Model Predictive Control and Health Monitoring System (ZMPC+HMS) AP algorithms, and their first evaluation in a supervised outpatient setting with frequent exercise. MATERIALS AND METHODS Adolescents with type 1 diabetes underwent 3 days of closed-loop control (CLC) in a hotel setting with the ZMPC+HMS algorithms on the Diabetes Assistant platform. Subjects engaged in twice-daily exercise, including soccer, tennis, and bicycling. Meal size (unrestricted) was estimated and entered into the system by subjects to trigger a bolus, but exercise was not announced. RESULTS Ten adolescents (11.9-17.7 years) completed 72 h of CLC, with data on 95 ± 14 h of sensor-augmented pump (SAP) therapy before CLC as a comparison to usual therapy. The percentage of time with continuous glucose monitor (CGM) 70-180 mg/dL was 71% ± 10% during CLC, compared to 57% ± 16% during SAP (P = 0.012). Nocturnal control during CLC was safe, with 0% (0%, 0.6%) of time with CGM <70 mg/dL compared to 1.1% (0.0%, 14%) during SAP. Despite large meals (estimated up to 120 g carbohydrate), only 8.0% ± 6.9% of time during CLC was spent with CGM >250 mg/dL (16% ± 14% during SAP). The system remained connected in CLC for 97% ± 2% of the total study time. No adverse events or severe hypoglycemia occurred. CONCLUSIONS The use of the ZMPC+HMS algorithms is feasible in the adolescent outpatient environment and achieved significantly more time in the desired glycemic range than SAP in the face of unannounced exercise and large announced meal challenges.
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What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia?
Harris, DL, Gamble, GD, Weston, PJ, Harding, JE
The Journal of pediatrics. 2017;:136-141
Abstract
OBJECTIVE To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth. STUDY DESIGN We analyzed data from 227 infants with hypoglycemia (blood glucose <46.8 mg/dL, 2.6 mmol/L) born at a tertiary hospital who experienced 295 episodes of hypoglycemia. Blood glucose concentrations were measured (glucose oxidase) within 90 minutes after randomization to dextrose or placebo gel plus feeding with formula, expressed breast milk, or breast feeding. RESULTS The overall mean increase in blood glucose concentration was 11.7 mg/dL (95% CI 10.4-12.8). The increase was greater after buccal dextrose gel than after placebo gel (+3.0 mg/dL; 95% CI 0.7-5.3; P = .01) and greater after infant formula than after other feedings (+3.8 mg/dL; 95% CI 0.8-6.7; P = .01). The increase in blood glucose concentration was not affected by breast feeding (+2.0 mg/dL; 95% CI -0.3 to 44.2; P = .09) or expressed breast milk (-1.4 mg/dL; 95% CI -3.7 to 0.9; P = .25). However, breast feeding was associated with reduced requirement for repeat gel treatment (OR = 0.52; 95% CI 0.28-0.94; P = .03). CONCLUSIONS Treatment of infants with hypoglycemia with dextrose gel or formula is associated with increased blood glucose concentration and breast feeding with reduced need for further treatment. Dextrose gel and breast feeding should be considered for first-line oral treatment of infants with hypoglycemia.
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Stabilization of glycemic control and improved quality of life using a shared medical appointment model in adolescents with type 1 diabetes in suboptimal control.
Floyd, BD, Block, JM, Buckingham, BB, Ly, T, Foster, N, Wright, R, Mueller, CL, Hood, KK, Shah, AC
Pediatric diabetes. 2017;(3):204-212
Abstract
BACKGROUND Declining glycemic control in type 1 diabetes (T1D) during adolescence persists despite treatment advances. Non-adherence, peer relations, diabetes burnout, risk taking, transition to autonomy, family conflict, and poor quality of life (QOL) are recognized barriers. Shared medical appointments (SMAs) in adolescent T1D may offer benefits, but data are limited. Our objective was to determine whether SMAs, with multi-component interventions utilizing multidisciplinary teams, improve glycemic control and psychosocial outcomes in poorly controlled adolescent T1D. METHODS SMAs focused on self-management, communication skills, goal setting, glucose pattern recognition, and peer/diabetes team support. SMAs included: individual history and physical, labs, surveys, multidisciplinary educational ice breakers, group session, and individual wrap up. Outcomes were QOL, adherence, and retrospective and prospective glycemic control. Three to six subjects and families came to 3 SMAs and 1 individual appointment every 3 months over 9 months. SUBJECTS A total of 37 English speaking subjects, ages 12-16 yrs, with T1D ≥ 1 year, and hemoglobin A1c (HbA1c) 7.5-11% enrolled. Thirty-two subjects attended 75% of visits, meeting inclusion criteria. RESULTS HbA1c worsened in the 9 months before study (ΔHbA1c= 0.7 ± 1.2; p < 0.01), but remained stable during study (ΔHbA1c = 0.01 ± 1.2; p > 0.05). There were significant improvements in overall QOL (p = 0.005), school function (p = 0.006), psychosocial function (p = 0.008), barriers (p = 0.02), adherence (p = 0.01), and communication (p = 0.02). Improvements in school function and communication reached clinical significance. CONCLUSION SMAs are feasible replacements to individual appointments in adolescent T1D, stabilizing glycemic control and improving QOL. Randomized controlled trials with optimizations are needed to further explore and refine this intervention.