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Transitional Hypoglycaemia Management in Small for Gestational Age Neonates with Sucrose Enriched Expressed Breastmilk in Resource Poor Setting.
Bora, R, Deori, S
Journal of tropical pediatrics. 2020;(3):267-274
Abstract
AIM: To find out if oral sucrose is as efficacious as intravenous dextrose (IVDx) in treating hypoglycaemia in small for gestational age (SGA) neonates and to compare risk of feed intolerance (FI) and necrotizing enterocolitis (NEC) in oral therapy with IVDx therapy. METHODS Eighty SGA haemodynamically stable hypoglycaemic [blood sugar (BS) < 40 mg/dl] neonates of ≥32 to ≤36 week gestational age were randomized to receive oral sugar enriched expressed breastmilk (EBM; Group A) or IV dextrose therapy (Group B; 40 in each group) in similar calculated doses. BS at 6 h after treatment, incidence of recurrence of hypoglycaemia, FI and NEC were compared. RESULTS Mean BS level at 6 h after treatment in oral supplementation group was 63.53 ± 22.12 mg/dl [3.52 ± 1.22 mmol/l (IQR 49.2-82 mg/dl, 2.7-4.5 mmol/l) vs. 71.28 ± 31.76 mg/dl [3.96 ± 1.76 mmol/l (IQR 48.5-73 mg/dl, 2.69-4 mmol/l) in IVDx group, p = 0.209. Relative risk (RR) of recurrence of hypoglycaemia in oral vs. IV treatment was 1.5 with 95% CI 0.4578-4.9151. Incidence of FI (p = 0.49, RR 1, 95%CI 0.3-3.1) and NEC (p = 0.4, RR 0.2, 95%CI 0.01-4.2) was comparable. CONCLUSION In resource poor setting in haemodynamically stable hypoglycaemic SGA neonates, EBM enriched with calculated dose of sucrose given orally maintains euglycaemia (BS 40-125mg/dl, 2.2-6.9 mmol/l) without increased incidence of FI and NEC. This method also prevents lactational failure.
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Trafficking of nonesterified fatty acids in insulin resistance and relationship to dysglycemia.
Walker, RE, Ford, JL, Boston, RC, Savinova, OV, Harris, WS, Green, MH, Shearer, GC
American journal of physiology. Endocrinology and metabolism. 2020;(3):E392-E404
Abstract
In adipose, insulin functions to suppress intracellular lipolysis and secretion of nonesterified fatty acid (NEFA) into plasma. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEFA-specific insulin resistance. We used total NEFA and individual fatty acids in the NEFA MM, comparing the model parameters in metabolic syndrome (MetSyn) subjects (n = 52) with optimally healthy controls (OptHC; n = 14). Results are reported as mean difference (95% confidence interval). Using the glucose MM, MetSyn subjects had lower [-73% (-82, -57)] sensitivity to insulin (Si) and higher [138% (44, 293)] acute insulin response to glucose (AIRg). Using the NEFA MM, MetSyn subjects had lower [-24% (-35, -13)] percent suppression, higher [32% (15, 52)] threshold glucose (gs), and a higher [81% (12, 192)] affinity constant altering NEFA secretion (ϕ). Comparing fatty acids, percent suppression was lower in myristic acid (MA) than in all other fatty acids, and the stearic acid (SA) response was so unique that it did not fit the NEFA MM. MA and SA percent of total were increased at 50 min after glucose injection, whereas oleic acid (OA) and palmitic acid (PA) were decreased (P < 0.05). We conclude that the NEFA MM, as well as the response of individual NEFA fatty acids after a FSIVGTT, differ between OptHC and MetSyn subjects and that the NEFA MM parameters differ between individual fatty acids.
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Severe hypoglycaemia and absolute risk of cause-specific mortality in individuals with type 2 diabetes: a UK primary care observational study.
Zaccardi, F, Ling, S, Lawson, C, Davies, MJ, Khunti, K
Diabetologia. 2020;(10):2129-2139
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AIMS/HYPOTHESIS Several pathophysiological mechanisms would suggest a causal link between hypoglycaemia and cardiovascular death; conversely, current knowledge would not support a causal relationship with other causes of death. To clarify the nature and the magnitude of the association between hypoglycaemia and death, we investigated the 5 year mortality risks for cardiovascular disease, cancer and other causes in individuals with type 2 diabetes admitted to hospital for a severe hypoglycaemic episode. METHODS We defined in the UK Clinical Practice Research Datalink database a prevalent cohort of adults with type 2 diabetes diagnosed between 1 January 1998 and 1 January 2011 (index date), with available linkage to the Office for National Statistics (ONS) and the Hospital Episode Statistics (HES). A hospital admission reporting hypoglycaemia as the underlying cause was identified before the index date in the HES; date and underlying cause of death were obtained from the ONS. We quantified the 5 year risk of cause-specific death in people with and without admission to hospital for severe hypoglycaemia, adjusting for potential confounders and accounting for competing risk. RESULTS Of the 74,610 subjects included in the cohort, 388 (0.5%) were admitted at least once for a severe hypoglycaemic episode; subjects admitted were older, with higher HbA1c and a greater prevalence of multimorbidity. During a median follow-up of 7.1 years, 236 (60.8%) and 18,539 (25.0%) deaths occurred in subjects with and without a previous severe hypoglycaemia, respectively. Non-cardiovascular causes accounted for 71% of all deaths in both subjects with and without hypoglycaemia. In a 60-year-old person with severe hypoglycaemia, the 5 year absolute risk of death, adjusted for age, sex, ethnicity, systolic blood pressure, total cholesterol, HbA1c, BMI, eGFR, smoking status, alcohol consumption and deprivation (Townsend score), was 6.6%, 1.1% and 13.1% for cardiovascular, cancer and other causes, respectively, while the 5 year absolute risk difference compared with a subject without severe hypoglycaemia was 4.7% (95% CI 1.0, 8.3) for cardiovascular, -1.4% (-4.1, 1.4) for cancer and 11.1% (6.1, 16.1) for other causes of death. Results were consistent in models further adjusted for medications and comorbidities (myocardial infarction, stroke, peripheral artery disease, heart failure, atrial fibrillation, cancer), with sulfonylurea and insulin associated with increased mortality rates (from cause-specific hazard ratio of 1.06 [95% CI 0.99, 1.14] for cancer death with use of sulfonylurea to 1.42 [1.29, 1.56] for cardiovascular death with use of insulin). Results were robust to missing data. CONCLUSIONS/INTERPRETATION The results of this study indicate severe hypoglycaemia as a marker of, rather than causally linked to, an increased risk of long-term mortality. Regardless of the nature of the association, a severe hypoglycaemic episode represents a strong negative prognostic factor in patients with type 2 diabetes. Graphical abstract.
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Influence of Fasting Glucose Levels on Achieving Glycemic Target in Individuals with Type 2 Diabetes: a Post Hoc Analysis.
Ma, J, Lei, M, Li, Y, Zhang, X, Cui, N, Yang, W
Advances in therapy. 2020;(9):3816-3826
Abstract
INTRODUCTION FPG GOAL was a 24-week, open-label, treat-to-target randomized controlled trial which demonstrated that the optimal self-monitored fasting blood glucose (SM-FBG) target for most Chinese individuals with type 2 diabetes (T2D) using insulin glargine 100 IU/mL was 3.9-6.1 mmol/L. Individuals who achieved lower fasting plasma glucose (FPG) levels might achieve the target HbA1c of < 7% without increasing the risk of hypoglycemia. METHODS For this post hoc analysis, individuals were redivided into three groups based on their actual laboratory FPG levels at 24 weeks: level 1, ≤ 5.6 mmol/L; level 2, > 5.6 to ≤ 6.1 mmol/L; and level 3, > 6.1 to ≤ 7.0 mmol/L. RESULTS At week 24, 863 individuals with diabetes had available FPG data and 179, 122, and 179 individuals achieved FPG levels 1, 2, and 3, respectively. The proportion of individuals with HbA1c < 7% or HbA1c < 7% without hypoglycemia (≤ 3.9 or ≤ 3.0 mmol/L) was significantly higher in FPG levels 1 (p < 0.01) and 2 (p < 0.05) than in level 3. The least squares mean changes from baseline in HbA1c (- 1.77% and - 1.66% vs - 1.34%; both p < 0.001) and 2-h postprandial glucose (- 3.88 mmol/L and - 3.98 mmol/L vs - 3.22 mmol/L; both p < 0.05) were also significantly higher in FPG levels 1 and 2 compared with level 3. Linear regression analysis showed a moderate relationship between FPG and HbA1c levels at 24 weeks (r = 0.449). CONCLUSIONS Chinese individuals with T2D who achieved lower FPG levels with insulin glargine 100 IU/mL were more likely to achieve the recommended target HbA1c of < 7% compared with those with higher FPG levels. ClinicalTrials.gov identifier NCT02545842.
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New hypoglycaemic therapy in frail older people with diabetes mellitus-phenotypic status likely to be more important than functional status.
Abdelhafiz, AH, Emmerton, D, Sinclair, AJ
Diabetes research and clinical practice. 2020;:108438
Abstract
Frail older people are largely excluded from clinical trials and therefore glycaemic targets and optimum hypoglycaemic therapy in this group has not been fully investigated. Guidelines generally recommend tight glycaemic control in functionally fit individuals and relaxed targets in frail ones mainly due to the fear of hypoglycaemia. The newly introduced sodium glucose cotransporter-2 inhibitors and the glucagon like peptide-1 receptor agonists have shown benefit that is independent of glycaemic control and a minimal risk of hypoglycaemia. However, guidelines still express caution about its use in frail older people due to fear of other side effects such as weight loss, hypotension and falls. Some frail older people will miss out on the benefits of this new therapy if frailty is considered as a one entity with a blanket application of guidelines. We propose that frailty should be viewed as two distinct metabolically different phenotypes, the sarcopenic-obese, in which new therapy will improve their metabolic profile and should be liberally used if no contraindications, and the anorexic-malnourished phenotype in which the new therapy should be cautiously considered. In other words, glycaemic targets should be driven by individual's overall function but the use of new therapy should be driven by frailty phenotype.
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The impact of strict COVID-19 lockdown in Spain on glycemic profiles in patients with type 1 Diabetes prone to hypoglycemia using standalone continuous glucose monitoring.
Mesa, A, Viñals, C, Pueyo, I, Roca, D, Vidal, M, Giménez, M, Conget, I
Diabetes research and clinical practice. 2020;:108354
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AIMS: Spain has been one of the worst affected countries by the COVID-19 pandemic. A very strict lockdown at home was imposed with a tough restriction of mobility. We aimed to evaluate the impact of this exceptional scenario on glucose profile of patients with T1D prone to hypoglycemia using standalone continuous glucose monitoring. METHODS Patients with T1D prone to hypoglycemia using multiple daily injections and either a Dexcom G5® or a Free Style Libre® CGM systems for at least 6 months under the funding of National Health Service were included in an observational, retrospective study. Data were collected in two periods: pre-lockdown (PL), February 23rd-March 7th and within lockdown (WL), April 1st-14th 2020. The primary outcome was the difference in the proportion of time in target glucose range of 70-180 mg/dL (TIR). Additional glucometric data were also analysed. RESULTS 92 patients were included: 40 women, age 42.8 ± 3.9 years, disease duration of 23.1 ± 12.6 years. Seventeen patients used Dexcom G5® and 75 Free Style Libre®. TIR 70-180 mg/dL (59.3 ± 16.2 vs 62.6 ± 15.2%), time > 180 (34.4 ± 18.0 vs 30.7 ± 16.9%), >250 (11.1 ± 10.6 vs 9.2 ± 9.7%) and Glucose Management Indicator (7.2 ± 0.8 vs 7.0 ± 0.8%) significantly improved (PL vs WL, respectively, p < 0.05). Time in hypoglycemia remained unchanged. CONCLUSIONS Lockdown conditions imposed by the COVID-19 pandemic may be managed successfully in terms of glycemic control by population with T1D prone to hypoglycemia using CGM. The strict daily routine at home could probably explain the improvement in the time in glycemic target without increasing the time in hypoglycemia.
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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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Nesidioblastosis Associated with Pancreatic Heterotopia as a Differential Diagnosis of Hypoglycemia: A Literature Review and Case Report.
Lopes, AA, Miranda, AC, Maior, MS, de Mello, RV, Bandeira, FA
The American journal of case reports. 2020;:e922778
Abstract
BACKGROUND Nesidioblastosis is a rare disease that is part of the differential diagnosis of pancreatogenic hyperinsulinemic hypoglycemia (PHH) in patients whose imaging studies do not localize insulinoma. Pancreatic heterotopia is a rare congenital abnormality characterized by pancreatic tissue anatomically separated from the main gland and found in 0.5% of abdominal surgeries. The purpose of this article is to provide a systematic review of the literature on nesidioblastosis in pancreatic ectopic tissue and to describe a case of the co-occurrence of these 2 rare conditions. CASE REPORT A 32-year-old man presented with adrenergic and neuroglycopenic symptoms, with laboratory-confirmed hyperinsulinemic hypoglycemia. There was no evidence of tumors on abdominal CT scan and MRI. Celiac trunk sampling with a calcium stimulation test was done, which showed an insulin gradient in the gastroduodenal artery. However, the intraoperative ultrasound showed a small nodule located at the pancreatic tail, leading to distal pancreatectomy. The histologic examination showed nesidioblastosis associated with pancreatic heterotopia. The patient remained asymptomatic after distal pancreatectomy. CONCLUSIONS Nesidioblastosis accounts for 0.5%-5% of all cases of PHH, with a histology showing hypertrophy and hyperplasia of pancreatic islets. Pancreatic heterotopia is a rare congenital anomaly resulting from failure of pancreatic cell migration, and is found as an incidentaloma in imaging or surgeries. Although it is a rare disease, nesidioblastosis should be considered in the investigation of hypoglycemia, even in the rare presentation of nesidioblastosis in patients with pancreatic heterotopy.
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A single-blind, randomised, crossover study to reduce hypoglycaemia risk during postprandial exercise with closed-loop insulin delivery in adults with type 1 diabetes: announced (with or without bolus reduction) vs unannounced exercise strategies.
Tagougui, S, Taleb, N, Legault, L, Suppère, C, Messier, V, Boukabous, I, Shohoudi, A, Ladouceur, M, Rabasa-Lhoret, R
Diabetologia. 2020;(11):2282-2291
Abstract
AIMS/HYPOTHESIS For individuals living with type 1 diabetes, closed-loop insulin delivery improves glycaemic control. Nonetheless, maintenance of glycaemic control during exercise while a prandial insulin bolus remains active is a challenge even to closed-loop systems. We investigated the effect of exercise announcement on the efficacy of a closed-loop system, to reduce hypoglycaemia during postprandial exercise. METHODS A single-blind randomised, crossover open-label trial was carried out to compare three strategies applied to a closed-loop system at mealtime in preparation for exercise taken 90 min after eating at a research testing centre: (1) announced exercise to the closed-loop system (increases target glucose levels) in addition to a 33% reduction in meal bolus (A-RB); (2) announced exercise to the closed-loop system and a full meal bolus (A-FB); (3) unannounced exercise and a full meal bolus (U-FB). Participants performed 60 min of exercise at 60% [Formula: see text] 90 min after eating breakfast. The investigators were not blinded to the interventions. However, the participants were blinded to the sensor glucose readings and to the insulin infusion rates throughout the intervention visits. RESULTS The trial was completed by 37 adults with type 1 diabetes, all using insulin pumps: mean±SD, 40.0 ± 15.0 years of age, HbA1c 57.1 ± 10.8 mmol/mol (7.3 ± 1.0%). Reported results were based on plasma glucose values. During exercise and the following 1 h recovery period, time spent in hypoglycaemia (<3.9 mmol/l; primary outcome) was reduced with A-RB (mean ± SD; 2.0 ± 6.2%) and A-FB (7.0 ± 12.6%) vs U-FB (13.0 ± 19.0%; p < 0.0001 and p = 0.005, respectively). During exercise, A-RB had the least drop in plasma glucose levels: A-RB -0.3 ± 2.8 mmol/l, A-FB -2.6 ± 2.9 mmol/l vs U-FB -2.4 ± 2.7 mmol/l (p < 0.0001 and p = 0.5, respectively). Comparison of A-RB vs U-FB revealed a decrease in the time spent in target (3.9-10 mmol/l) by 12.7% (p = 0.05) and an increase in the time spent in hyperglycaemia (>10 mmol/l) by 21% (p = 0.001). No side effects were reported during the applied strategies. CONCLUSIONS/INTERPRETATION Combining postprandial exercise announcement, which increases closed-loop system glucose target levels, with a 33% meal bolus reduction significantly reduced time spent in hypoglycaemia compared with the other two strategies, yet at the expense of more time spent in hyperglycaemia. TRIAL REGISTRATION ClinicalTrials.gov NCT0285530 FUNDING JDRF (2-SRA-2016-210-A-N), the Canadian Institutes of Health Research (354024) and the Fondation J.-A. DeSève chair held by RR-L.
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Closed-loop insulin delivery in adults with type 1 diabetes in real-life conditions: a 12-week multicentre, open-label randomised controlled crossover trial.
Benhamou, PY, Franc, S, Reznik, Y, Thivolet, C, Schaepelynck, P, Renard, E, Guerci, B, Chaillous, L, Lukas-Croisier, C, Jeandidier, N, et al
The Lancet. Digital health. 2019;(1):e17-e25
Abstract
BACKGROUND Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy. METHODS In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA1c) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556. FINDINGS Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error. INTERPRETATION The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes. FUNDING French Innovation Fund, Diabeloop.