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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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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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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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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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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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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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Interstitial glucose concentrations and hypoglycemia during 2 days of caloric deficit and sustained exercise: a double-blind, placebo-controlled trial.
Smith, TJ, Wilson, MA, Karl, JP, Austin, K, Bukhari, A, Pasiakos, SM, O'Connor, KL, Lieberman, HR
Journal of applied physiology (Bethesda, Md. : 1985). 2016;(5):1208-1216
Abstract
Military personnel and some athlete populations endure short-term energy deficits from reduced energy intake and/or increased energy expenditure (EE) that may degrade physical and cognitive performance due to severe hypoglycemia (<3.1 mmol/l). The extent to which energy deficits alter normoglycemia (3.9-7.8 mmol/l) in healthy individuals is not known, since prior studies measured glucose infrequently, not continuously. The purpose of this study was to characterize the glycemic response to acute, severe energy deficit compared with fully fed control condition, using continuous glucose monitoring (CGM). For 2 days during a double-blind, placebo-controlled, crossover study, 23 volunteers (17 men/6 women; age: 21.3 ± 3.0 yr; body mass index: 25 ± 3 kg/m) increased habitual daily EE [2,300 ± 450 kcal/day [means ± SD)] by 1,647 ± 345 kcal/day through prescribed exercise (~3 h/day; 40-65% peak O2 consumption), and consumed diets designed to maintain energy balance (FED) or induce 93% energy deficit (DEF). Interstitial glucose concentrations were measured continuously by CGM (Medtronic Minimed). Interstitial glucose concentrations were 1.0 ± 0.9 mmol/l lower during DEF vs. FED (P < 0.0001). The percentage of time spent in mild (3.1-3.8 mmol/l) hypoglycemia was higher during DEF compared with FED [mean difference = 20.5%; 95% confidence interval (CI): 13.1%, 27.9%; P = 0.04], while time spent in severe (<3.1 mmol/l) hypoglycemia was not different between interventions (mean difference = 4.6%; 95% CI: -0.6%, 9.8%; P = 0.10). Three of 23 participants spontaneously reported symptoms (e.g., nausea) potentially related to hypoglycemia during DEF, and an additional participant reported symptoms during both interventions. These findings suggest that severe hypoglycemia rarely occurs in healthy individuals enduring severe, short-term energy deficit secondary to heavy exercise and inadequate energy intake.
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Blood Glucose Levels of Subelite Athletes During 6 Days of Free Living.
Thomas, F, Pretty, CG, Desaive, T, Chase, JG
Journal of diabetes science and technology. 2016;(6):1335-1343
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BACKGROUND Continuous glucose monitoring (CGM) devices, with their 1-5 min measurement interval, allow blood glucose (BG) concentration dynamics to be captured more frequently and less invasively than traditional BG measures. One cohort CGM could provide insight is athletes. This study investigates what impact their heightened energy expenditure and dietary intake may have on their ability to achieve optimal BG. METHODS Ten subelite athletes (resting HR<60 bpm, training>6 hrs per week) were recruited. Two Ipro2 CGM devices (Medtronic Minimed, Northridge, CA) were inserted into the abdomen and remained in place for ~6 days. Time in band was calculated as the percentage of CGM BG measurements with in the 4.0-6.0 mmol/L. Fasting glucose was calculated using CGM calibration BG measurements and postprandial glucose response was also calculated using the CGM values. RESULTS 4/10 athletes studied spent more than 70% of the total monitoring time above 6.0 mmol/L even with the 2-hour period after meals is excluded. Fasting BG was also in the ADA defined prediabetes range for 3/10 athletes. Only 1 participant spent substantial time below 4.0 mmol/L which was largely due to significantly lower energy intake compared to recommendations. CONCLUSIONS Contrary to expectations high BG appears to be more of a concern for athletes then low BG even in those with the highest energy expenditure and consuming below the recommended carbohydrate intake. This study warrants further investigation on the recommended diets and the BG of athletes to better determine the causes and impact of this hyperglycemia on overall athlete health.
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Hypoglycemia Detection and Carbohydrate Suggestion in an Artificial Pancreas.
Turksoy, K, Kilkus, J, Hajizadeh, I, Samadi, S, Feng, J, Sevil, M, Lazaro, C, Frantz, N, Littlejohn, E, Cinar, A
Journal of diabetes science and technology. 2016;(6):1236-1244
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Fear of hypoglycemia is a major concern for many patients with type 1 diabetes and affects patient decisions for use of an artificial pancreas system. We propose an alternative way for prevention of hypoglycemia by issuing predictive hypoglycemia alarms and encouraging patients to consume carbohydrates in a timely manner. The algorithm has been tested on 6 subjects (3 males and 3 females, age 24.2 ± 4.5 years, weight 79.2 ± 16.2 kg, height 172.7 ± 9.4 cm, HbA1C 7.3 ± 0.48%, duration of diabetes 209.2 ± 87.9 months) over 3-day closed-loop clinical experiments as part of a multivariable artificial pancreas control system. Over 6 three-day clinical experiments, there were only 5 real hypoglycemia episodes, of which only 1 hypoglycemia episode occurred due to being missed by the proposed algorithm. The average hypoglycemia alarms per day and per subject was 3. Average glucose value when the first alarms were triggered was recorded to be 117 ± 30.6 mg/dl. Average carbohydrate consumption per alarm was 14 ± 7.8 grams. Our results have shown that most low glucose concentrations can be predicted in advance and the glucose levels can be raised back to the desired levels by consuming an appropriate amount of carbohydrate. The proposed algorithm is able to prevent most hypoglycemic events by suggesting appropriate levels of carbohydrate consumption before the actual occurrence of hypoglycemia.
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Pilot study of the SPRINT glycemic control protocol in a Hungarian medical intensive care unit.
Benyo, B, Illyés, A, Némedi, NS, Le Compte, AJ, Havas, A, Kovacs, L, Fisk, L, Shaw, GM, Chase, JG
Journal of diabetes science and technology. 2012;(6):1464-77
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INTRODUCTION Stress-induced hyperglycemia increases morbidity and mortality. Tight control can reduce mortality but has proven difficult to achieve. The SPRINT (Specialized Relative Insulin and Nutrition Tables) protocol is the only protocol that reduced both mortality and hypoglycemia by modulating both insulin and nutrition, but it has not been tested in independent hospitals. METHODS SPRINT was used for 12 adult intensive care unit patients (949 h) at Kálmán Pándy Hospital (Gyula, Hungary) as a clinical practice assessment. Insulin recommendations (0-6 U/h) were administered via constant infusion rather than bolus delivery. Nutrition was administered per local standard protocol, weaning parenteral to enteral nutrition, but was modulated per SPRINT recommendations. Measurement was every 1 to 2 h, per protocol. Glycemic performance is assessed by percentage of blood glucose (BG) measurements in glycemic bands for the cohort and per patient. Safety from hypoglycemia is assessed by numbers of patients with BG < 2.2 (severe) and %BG < 3.0 and < 4.0 mmol/liter (moderate and light). Clinical effort is assessed by measurements per day. Results are median (interquartile range). RESULTS There were 742 measurements over 1088 h of control (16.4 measurements/day), which is similar to clinical SPRINT results (16.2/day). Per-patient hours of control were 65 (50-95) h. Initial per-patient BG was 10.5 (7.9-11.2) mmol/liter. All patients (100%) reached 6.1 mmol/liter. Cohort BG was 6.3 (5.5-7.5) mmol/liter, with 42.2%, 65.1% and 77.6% of BG in the 4.0-6.1, 4.0-7.0, and 4.0-8.0 mmol/liter bands. Per-patient, median percentage time in these bands was 40.2 (26.7-51.5)%, 62.5 (46.0-75.7)%, and 74.7 (61.6.8-87.8)%, respectively. No patients had BG < 2.2 mmol/liter, and the %BG < 4.0 mmol/liter was 1.9%. These results were achieved using 3.0 (3.0-5.0) U/h of insulin with 7.4 (4.4-10.2) g/h of dextrose administration (all sources) for the cohort. Per-patient median insulin administration was 3.0 (3.0-3.0) U/h and 7.1 (3.4-9.6) g/h dextrose. Higher carbohydrate nutrition formulas than were used in SPRINT are offset by slightly higher insulin administration in this study. CONCLUSIONS The glycemic performance shows that using the SPRINT protocol to guide insulin infusions and nutrition administration provided very good glycemic control in initial pilot testing, with no severe hypoglycemia. The overall design of the protocol was able to be generalized with good compliance and outcomes across geographically distinct clinical units, patients, and clinical practice.
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The dry plant extract of common bean seed (Phaseoli vulgari pericarpium) does not have an affect on postprandial glycemia in healthy human subject.
Cerović, A, Miletić, I, Konić-Ristić, A, Baralić, I, Djordjević, B, Djuricić, I, Radusinović, M
Bosnian journal of basic medical sciences. 2006;(3):28-33
Abstract
The aim of present study was to assess the effects and safety of a dry Phaseoli vulgari pericarpium (PVP) extract on postprandial glycemia in healthy participants. A randomized crossover experiment where participants received either PVP extract or placebo. Chemical compounds in dry extract were assessed by established methods. Eighteen healthy participants (9 male and 9 female) aged 29+/-4,8 years, body mass index (BMI) 23+/-3,7 kg/m(2) were recruited among students and staff at the Faculty of Pharmacy, University of Belgrade. All participants were able to follow the study protocol without difficulty. The participants received either PVP extract or placebo 30 minutes before a 50g oral glucose tolerance test (OGTT). The protocol followed the guidelines for the OGTT with blood samples drawn at 0, 15, 30, 60, 90 and 120 min. This study demonstrated that there was no significantly effect of the PVP extract on incremental blood glucose (IBG) and their areas under the curve (AUC) neither male nor female participants. However, IBG together with AUC changes were significantly lower in male compared with female participants in treated and untreated groups. The presence of chrome, soluble fiber, vitamin C, protein, glucose and lectins were also quantified. The applied amount of PVP extract was unable to produce the postprandial hypoglycemia. We assumed that amounts of chrome, soluble fiber, vitamin C which have beneficial effects on diabetes treatment were sufficient to produce hypoglycemia.
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Relationship of family history of type 2 diabetes, hypoglycemia, and autoantibodies to weight gain and lipids with intensive and conventional therapy in the Diabetes Control and Complications Trial.
Purnell, JQ, Dev, RK, Steffes, MW, Cleary, PA, Palmer, JP, Hirsch, IB, Hokanson, JE, Brunzell, JD
Diabetes. 2003;(10):2623-9
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Intensive therapy for type 1 diabetes results in greater weight gain than conventional therapy. Many factors may predispose to this greater weight gain, including improved glycemic control, genetic susceptibility to obesity, and hypoglycemia. To study this, relationships among family history of type 2 diabetes, frequency of severe hypoglycemia, beta-cell autoantibodies, and weight gain were examined in 1,168 subjects aged > or =18 years at baseline randomized to intensive and conventional therapy groups in the Diabetes Control and Complications Trial. With intensive therapy, subjects with a family history of type 2 diabetes had greater central weight gain and dyslipidemia characterized by higher triglyceride levels and greater cholesterol in VLDLs and intermediate-density lipoproteins compared with subjects with no family history. Neither the frequency of severe hypoglycemia nor positivity to GAD65 and insulinoma-associated protein 2 antibodies was associated with increased weight gain with either intensive or conventional therapy. These data support the hypothesis that increased weight gain with intensive therapy might be explained, in part, by genetic traits.