Nocturnal Hypoglycemia In Type Research Articles

Nocturnal Hypoglycemia in Type 1 Diabetes “Do Parents Know How to Prevent?”:A Descriptive Study

Amaç: Araştırma 6-18 yaş grubu tip 1 diyabetli çocuk ve ergenlerin ebeveynlerinin gece hipoglisemisinin önlenmesiyle ilgili bilgi
 durumunun değerlendirmek amacıyla gerçekleştirilmiştir.
 Gereç ve Yöntemler: Tanımlayıcı tasarımdaki araştırma, Ocak-Mayıs 2018 tarihleri arasında İstanbul ilindeki dört hastanenin pediatrik
 endokrinoloji polikliniklerinde takipli 150 tip 1 diyabetli çocuk ve ergenin ebeveynleri ile gerçekleştirilmiştir. Araştırmanın verileri
 Ebeveyn Tanıtıcı Bilgi Formu ve Ebeveyn Hipoglisemi Bilgi Düzeyi Formu’ndan yararlanılarak toplanmıştır. Verilerin analizinde
 tanımlayıcı istatistikler ve Mann Whitney U testi kullanılmıştır.
 Bulgular: Katılımcıların yaş ortalaması 39,23±7,205 olup, çocuklarının diyabet yaşı 5,17±3,75’tir. Katılımcıların %78,7(n=118)’si gece
 hipoglisemilerine yönelik eğitim almıştır. Gece hipoglisemisine yönelik bilginin büyük oranda (%65,3; n=98) hemşireden alındığı
 saptanmıştır. Gece hipoglisemisi durumunda yapılan ilk uygulamanın sıklıkla (%45,3; n=68) kilosuna göre hızlı etkili karbonhidrat
 vermek ve hemen kan glikozu ölçümü yapmak (%43,3; n=65) olduğu görülmüştür. Katılımcıların gece hipoglisemisi ile ilgili bilgi
 düzeylerinin değerlendirildiği forma verdikleri doğru yanıt oranı %60 olarak saptanmıştır. Ebeveyn hipoglisemi bilgi durumu formu
 toplam puanı ile gece hipoglisemisi ile ilgili eğitim alanlar arasında istatistiksel olarak anlamlı fark saptanmıştır (U=1101, p

Nocturnal hypoglycemia in type 1 and type 2 diabetes: an update on prevalence, prevention, pathophysiology and patient awareness

ABSTRACT Introduction Despite considerable progress in diabetes treatment, prevalence of nocturnal hypoglycemia in type 1 diabetes mellitus (T1DM) and advanced insulin treated type 2 diabetes mellitus (T2DM) remains high. Areas covered The present manuscript describes the prevalence of night-time hypoglycemia as reported in observational and randomized controlled trials. Factors that affect the risk of hypoglycemia are highlighted. The authors also describe impaired awareness of hypoglycemia and available preventive methods. Expert opinion Prevention of nocturnal hypoglycemia includes behavioral, dietary and pharmacologic interventions. The most recent development with the lowest rate of hypoglycemia is sensor-augmented pumps with predictive low glucose suspend technology. These pumps combine continuous subcutaneous insulin infusion with continuous glucose monitoring and use various algorithms to predict and stop hypoglycemia before it develops.

Predicting and Preventing Nocturnal Hypoglycemia in Type 1 Diabetes Using Big Data Analytics and Decision Theoretic Analysis.

Background: Despite new glucose sensing technologies, nocturnal hypoglycemia is still a problem for people with type 1 diabetes (T1D) as symptoms and sensor alarms may not be detected while sleeping. Accurately predicting nocturnal hypoglycemia before sleep may help minimize nighttime hypoglycemia. Methods: A support vector regression (SVR) model was trained to predict, before bedtime, the overnight minimum glucose and overnight nocturnal hypoglycemia for people with T1D. The algorithm was trained on continuous glucose measurements and insulin data collected from 124 people (22,804 valid nights of data) with T1D. The minimum glucose threshold for announcing nocturnal hypoglycemia risk was derived by applying a decision theoretic criterion to maximize expected net benefit. Accuracy was evaluated on a validation set from 10 people with T1D during a 4-week trial under free-living sensor-augmented insulin-pump therapy. The primary outcome measures were sensitivity and specificity of prediction, the correlation between predicted and actual minimum nocturnal glucose, and root-mean-square error. The impact of using the algorithm to prevent nocturnal hypoglycemia is shown in-silico. Results: The algorithm predicted 94.1% of nocturnal hypoglycemia events (<3.9 mmol/L, 95% confidence interval [CI], 71.3-99.9) with an area under the receiver operating characteristic curve of 0.86 (95% CI, 0.75-0.98). Correlation between actual and predicted minimum glucose was high (R = 0.71, P < 0.001). In-silico simulations showed that the algorithm could reduce nocturnal hypoglycemia by 77.0% (P = 0.006) without impacting time in target range (3.9-10 mmol/L). Conclusion: An SVR model trained on a big data set and optimized using decision theoretic criterion can accurately predict at bedtime if overnight nocturnal hypoglycemia will occur and may help reduce nocturnal hypoglycemia.

Value of Capillary Glucose Profiles in Assessing Risk of Nocturnal Hypoglycemia in Type1 Diabetes Based on Continuous Glucose Monitoring.

IntroductionThis study aimed to evaluate the occurrence of nocturnal hypoglycemia in type 1 diabetes (T1D) based on continuous glucose monitoring (CGM), and to explore the value of capillary glucose profiles in assessing the risk of nocturnal hypoglycemia. The study also intended to develop a predictive model to identify people with high risk of nocturnal hypoglycemia.MethodsA total of 169 participants with T1D received 3 days of blinded CGM; meanwhile, their self-monitoring blood glucose (SMBG) profiles were recorded. Logistic regression analyses were used to evaluate contributory factors of nocturnal hypoglycemia. Potential indicators were estimated using area under receiver operator curve (AUC) analyses.ResultsDuring the retrospective CGM period, 95 (56.2%) participants with T1D reported 238 events of hypoglycemia, and 69 (29.0%) of these episodes occurred during the nighttime. Increased risk of nocturnal hypoglycemia correlated with lower HbA1c, glycated albumin, and mean blood glucose (OR = 0.790, 0.940, 0.651, respectively; P < 0.05) and higher standard deviation, mean amplitude of glycemic excursions, and low blood glucose index (OR = 1.463, 1.168, 4.035, respectively; P < 0.05) after adjustment for age and duration. Of the daily SMBG profiles, fasting blood glucose (OR = 0.643, P = 0.001) and blood glucose at bedtime (OR = 0.851, P = 0.037) were associated with the occurrence of nocturnal hypoglycemia. The BGn model, which was derived from the variation of capillary glucose, could discriminate individuals with increased risk of nocturnal hypoglycemia (AUC = 0.774).ConclusionsNocturnal hypoglycemia constitutes nearly one-third of hypoglycemic events in people with T1D. Strict glycemic control and great fluctuation of glucose are potential contributory factors. Daily SMBG profiles and the BGn model could help assess the risk of nocturnal hypoglycemia in T1D, which may support further development of preventive strategies.

Type 1 Diabetes in Children and Adolescents.

Type 1 Diabetes in Children and Adolescents.

Preventive effect of ipragliflozin on nocturnal hypoglycemia in patients with type 2 diabetes treated with basal-bolus insulin therapy: An open-label, single-center, parallel, randomized control study.

The efficacy of the administration of sodium‐glucose co‐transporter 2 inhibitor or the co‐administration of sodium‐glucose co‐transporter 2 inhibitor and dipeptidyl peptidase‐4 inhibitor to insulin therapy is not well known. A total of 58 patients with type 2 diabetes, admitted for glycemic control, were randomized to basal–bolus insulin therapy (BBT) alone or BBT plus 50 mg ipragliflozin and/or 20 mg teneligliptin. Insulin doses were adjusted to maintain normal blood glucose levels. Plasma glucose profiles were estimated by continuous glucose monitoring before discharge. Required insulin doses were not significantly different among the treatment groups. The frequency of nocturnal hypoglycemia was significantly lower in the groups treated with ipragliflozin (6.5 ± 10.6%) and ipragliflozin plus teneligliptin (6.9 ± 14.3%) than in the group treated with BBT alone (42 ± 43.6%). The administration of sodium‐glucose co‐transporter 2 inhibitor with or without dipeptidyl peptidase‐4 inhibitor prevented nocturnal hypoglycemia in type 2 diabetes patients with BBT.

A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes.

OBJECTIVEOvernight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.RESEARCH DESIGN AND METHODSFollowing an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15–45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred.RESULTSOvernight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43–0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.CONCLUSIONSUse of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.

Abstracts from ATTD 20147th International Conference on AdvancedTechnologies &amp; Treatments for DiabetesVienna, Austria, February 5–8, 2014

Introduction: Currently measures of glycaemic variability (Standard Deviation, Mean and MAGE) all fail to fully highlight the extent of blood glucose variability so there is a need for improved measures of glycaemic variability. Aim: To utilise clinical data produced using CGMS to develop and validate a clinically-relevant novel measure of glycaemic variability and to use it to compare CSII with MDI. Methods: 20 participants (6 months pre and post CSII) with 24 hr CGM data sets were analysed. Glucose variability Rating (GVR) was calculated in three steps including change in sensor reading at 5 minute intervals which were then squared and av- eraged to obtain GVR (mmol/L) 2/hr. GVR was plotted, area under curve (AUC) calculated and pre vs. post-CSII GVR compared. Time series analysis was also investigated to try and identify specific periods with increased variability. A compari- son of the percentage change in GVR vs the change in HbA1c value in pre vs post-CSII was also analysed to identify correla- tion between these two measures. Results: GVR was applied to pre and post-CSII CGM data; 75% of participants showed < 20% reduction of GVR post-CSII vs. MDI. The group also showed a significant reduction in GVR (p < 0.003) post-CSII (vs MDI). Conclusions: Results indicate a reduction in glucose vari- ability with CSII and highlight the limitations of HbA1c, as well as the useful potential of GVR to highlight specific time periods where intervention is required to control blood glucose variability.

Insulin pumps with a sensor and threshold-suspend reduced nocturnal hypoglycemia in type 1 diabetes

Source Citation Bergenstal RM, Klonoff DC, Garg SK, et al; ASPIRE In-Home Study Group. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013;369:224-32. 23789889

Efficacy and safety of degludec insulin: a meta-analysis of randomised trials

Objectives:Degludec is a novel long-acting insulin analogue, providing an adequate supply of basal insulin over 24 hours with one daily injection, with a supposed greater reproducibility and flexibility than other basal insulins.Methods:An extensive search of Medline and the Cochrane Library for ‘degludec’ was performed, up to July 1st, 2012, collecting all randomised trials with a duration of at least 16 weeks and enrolling patients with diabetes. The principal outcome was the effect of degludec, compared with other basal insulins, on endpoint HbA1c and hypoglycaemia. Secondary outcomes included BMI, FPG at endpoint, and the incidence of cardiovascular events and cancer.Results:In the four trials comparing degludec with glargine, endpoint HbA1c was similar in the two groups, whereas FPG was significantly lower in degludec-treated patients. Degludec was associated with a lower rate of overall and nocturnal hypoglycaemia in type 2 and type 1 diabetes, respectively. No differences were observed for cardiovascular events and cancer.Study limitations:The number of available trials and the duration of exposure were limited, so the results obtained should be considered preliminary.Conclusions:Degludec appears to be associated with a lower incidence of hypoglycaemia in comparison with glargine, for similar levels of glycaemic control. The use of this agent could represent one step further in insulin therapy.

Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review.

BackgroundInsulin degludec (IDeg) is a neutral, ultralong-acting new generation basal insulin analog developed by NovoNordisk currently in Phase III clinical development. IDeg offers a duration of action of more than 42 hours in adults, much longer than current basal insulin formulations.ObjectiveThe aim of this review is to assess the efficacy and safety data of IDeg in the treatment of type 1 and type 2 diabetes mellitus.MethodsRelevant English language articles from 2010 to 2012 were identified through MEDLINE, PubMed, EMBASE, Scopus, BIOSIS, and Google Scholar. Online conference proceedings of the 71st ADA Scientific Sessions and the 47th EASD Annual Meeting were reviewed. Studies were compared in terms of their study designs, primary and secondary efficacy parameters, and tolerability data.ResultsThere are a total of nine published trials investigating the clinical efficacy and safety of IDeg in over 3000 subjects with type 1 and 2 diabetes. Only three trials were published in full. All were open-label, randomized multicenter trials with durations of 16 to 52 weeks. IDeg and coformulations of IDeg with insulin aspart (IAsp) were compared to insulin glargine (IGlar), detemir, and biphasic IAsp 30 (BIAsp 30).ConclusionBased upon the available evidence, there appear to be no reported differences between IDeg and IGlar, detemir, or BIAsp 30 in the reduction of the primary efficacy end-points of HbA1c and mean fasting plasma glucose (FPG) concentrations. Only flexible dosing of IDeg provided a significant reduction in FPG compared to IGlar. IDeg demonstrated a significant reduction in nocturnal hypoglycemia in type 1 diabetes. In type 2 diabetes, IDeg reduced the incidence of hypoglycemia by 18% and 58% compared to IGlar and BIAsp 30, respectively.

Delayed Nocturnal Hypoglycemia In Type 1 Diabetic Patients: Effect Of Two Different Exercise Modalities

Exercise is a cornerstone of diabetes management as it aids in glycemic control in type 1 diabetic patients (DMT1). The type of exercise is important in determining the propensity to experience hypoglycaemia. PURPOSE: To assess, by continuous glucose monitoring (CGM), the glucose variability and the possible hypoglycemic episodes before, during and in the following 24 hours after a session of two different types of exercise. METHODS: Eight healthy, physically active, non-trained, male volunteers with well-controlled DMT1 were studied [age 34±7 yr, body mass index (BMI) 24.0±2.2 kg/m2, HbA1c 7.14±0.6, insulin dosage 0.6±0.2 U/kg/day, VO2max 33.7± 6.1 ml·kg-1·min-1, duration of diabetes 14.3±8yr (mean±SD)]. They underwent to 30 min. of both intermittent high intensity exercise (IHE) and moderate intensity exercise (MOD) in random order. Expired air was recorded during the exercise, while metabolic and hormonal determinations were performed before and for 120 min after exercises. CGM system and activity monitor were applied for the subsequent 19 hours. RESULTS: Blood glucose declined during both type of exercise. At 150 min following the start of exercise, plasma glucose tended to be higher, although not significantly, after IHE. No changes were observed in plasma insulin concentration. A significant increase of norepinephrine concentration was noticed during IHE respect to MOD (peak values: 1016.3±154 vs 680.0±84.5pg/mL; p<0.05) while no differences were observed in epinephrine levels. During nighttime glucose levels were significantly lower after IHE than those observed after MOD exercise (147±17 vs 225±31mg/dl at 3:00AM, p<0.05). Moreover, the number of hypoglycemic episodes after IHE was significantly higher than that observed after MOD (2 in MOD vs 7 and IHE). CONCLUSIONS: We demonstrate a previously unrecognized phenomenon: despite slightly higher plasma glucose values in the early post-exercise, IHE is associated with a higher risk of delayed nocturnal hypoglycemia respect to MOD. These data suggest that CGM can be a useful approach in Type 1 diabetic patients who undergo to an exercise program.

Use of slow release starch (SRS) to treat hypoglycaemia in type 1 diabetics

PurposeThe purpose of this paper is to evaluate if slow release starch (SRS) could be used to control/limit hypoglycaemia in type 1 diabetics.Design/methodology/approachTen type‐1 diabetic volunteers were fitted with continuous glucose monitors for two periods of 3 days when undertaking their normal routine or when consuming 60 g SRS before sleep.FindingsThe average number of nocturnal hypoglycaemic episodes where no SRS was consumed over 3 days was 2.7 ± 2.0 but only 0.7 ± 1.1 after SRS consumption before sleep. The duration of these events was equivalent to 318 ± 282 and 140 ± 337 min, respectively. Average nocturnal blood glucose concentration was 7.9 ± 1.4 mmol l−1 without SRS consumption but increased to 9.7 ± 2.7 mmol l−1 when SRS was consumed. These data were highly significant when subjected to analysis of variance (ANOVA) test on a subject by subject basis. The SRS may be used as a cost effective therapy to avoid hypoglycaemia in patients with type‐1 diabetes.Originality/valueThis paper reports for the first time the use of a physically modified waxy maize starch (SRS) to prevent/limit the incidence of nocturnal hypoglycaemia in type 1 diabetics.

Nocturnal hypoglycaemia in type 1 diabetes--frequency and predictive factors

Nocturnal hypoglycaemia (NH) remains a problem in type 1 diabetes and spontaneous asymptomatic NH may be a risk factor for sudden death ('Dead in Bed' syndrome). To explore whether any predictive relationship exists between the average or time-specific glycaemia and the occurrence of NH. Twenty-five healthy patients with type 1 diabetes underwent two separate overnight periods of continuous glucose monitoring (CGM) using a MMT-7002 Medtronic MiniMed System. There was a 6-week interval before the second monitoring period. CGM glucose levels recorded between 23:00 and 08:00 h defined the nocturnal period and recorded glucose monitoring levels <3.5 mmol/l for at least 10 min during this time-defined NH. A CGM recording at 23:00 h and 08:00 h were taken as the bedtime and fasting glucose levels, respectively. The mean +/- SD age was 37 +/- 7 years and duration of diabetes 13 +/- 7 years; 16 (64%) were on long-acting analogue insulin. Forty-nine CGM data sets were recorded. Fourteen episodes of NH occurred in 12 patients (Group 1), 13 patients (Group 2) had no NH. Group 1 (NH) had a lower mean bedtime glucose recorded compared with Group 2 (7.7 +/- 4.3 vs. 11.4 +/- 4.0 mmol/l, P = 0.0035). Fasting glucose level was also lower in Group 1 following the occurrence of NH (P = 0.014). There was no difference in the type of insulin used between the two groups. Our data show that in normal day to day settings, NH is common and that the bedtime glucose level is a significant predictive factor.

Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes—the ‘dead in bed’ syndrome revisited

Sudden nocturnal death in type 1 diabetes ('dead in bed' syndrome) is thought to be due to ECG QT prolongation with subsequent ventricular tachyarrhythmia in response to nocturnal hypoglycaemia. We investigated this theoretical mechanism using continuous ECG and continuous glucose monitoring in a group of patients with type 1 diabetes. Twenty-five patients with type 1 diabetes (age 20-50 years) underwent two separate 24 h ECG and continuous glucose monitoring periods. Patients were fully ambulant and carried out normal daily activities. There were 13 episodes (26% of recordings) of nocturnal hypoglycaemia, eight of <2.2 mmol/l and five of 2.2-3.4 mmol/l. Corrected QT interval (QTc) was longer during nocturnal hypoglycaemia compared with normoglycaemic control periods (445 +/- 40 vs 415 +/- 23 ms; p = 0.037). Cardiac rate and rhythm disturbances (excluding sinus tachycardia) were seen in eight of the 13 nocturnal hypoglycaemia episodes (62%). These were sinus bradycardia (<40 beats/min; three episodes), ventricular ectopics (three episodes), atrial ectopics (one) and P wave abnormalities (one). This study demonstrates QTc prolongation and cardiac rate/rhythm disturbances in response to episodes of nocturnal hypoglycaemia in ambulant patients with type 1 diabetes. This may support an arrhythmic basis for the 'dead in bed' syndrome.

Terbutaline and the Prevention of Nocturnal Hypoglycemia in Type 1 Diabetes

OBJECTIVE—Bedtime administration of 5.0 mg of the β2-adrenergic agonist terbutaline prevents nocturnal hypoglycemia but causes morning hyperglycemia in type 1 diabetes. We tested the hypothesis that 2.5 mg terbutaline prevents nocturnal hypoglycemia without causing morning hyperglycemia.RESEARCH DESIGN AND METHODS—This was a randomized double-blind crossover pilot study (placebo, 2.5 mg terbutaline, and 5.0 mg terbutaline) in 15 patients with type 1 diabetes.RESULTS—Mean ± SE nadir nocturnal plasma glucose concentrations were 87 ± 14 mg/dl following placebo, 100 ± 14 mg/dl following 2.5 mg terbutaline, and 122 ± 13 mg/dl following 5.0 mg terbutaline (P < 0.05 vs. placebo). Nadir levels were <50 mg/dl in 5, 2, and 0 patients (P < 0.05 vs. placebo), respectively. Morning levels were 113 ± 18, 127 ± 17, and 183 ± 19 mg/dl (P < 0.02 vs. placebo), respectively.CONCLUSIONS—Terbutaline may be shown to be effective and safe in the prevention of nocturnal hypoglycemia in type 1 diabetes in a suitably powered randomized controlled trial.

Nocturnal hypoglycaemia in Type 1 diabetic patients, assessed with continuous glucose monitoring: frequency, duration and associations

We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple-injection therapy (MIT) using a continuous subcutaneous glucose sensor. A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA(1c) 7.8 +/- 0.9%) and 33 patients on MIT (HbA(1c) 8.7 +/- 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA(1c), diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated. Nocturnal hypoglycaemia < or = 3.9 mmol/l occurred in 33.3% of both the CSII- (8/24) and MIT-treated patients (11/33). Mean (+/- sd; median, interquartile range) duration of hypoglycaemia < or = 3.9 mmol/l was 78 (+/- 76; 57, 23-120) min per night for the CSII- and 98 (+/- 80; 81, 32-158) min per night for the MIT-treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia. Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.

Nocturnal Hypoglycemia in Type 1 Diabetes: An Assessment of Preventive Bedtime Treatments

We assessed four putative bedtime treatments in the prevention of nocturnal hypoglycemia in type 1 diabetes. Plasma glucose concentrations were measured every 15 min from 2200 h through 0700 h in 21 patients with type 1 diabetes (mean +/- sd HbA(1C) = 7.1 +/- 1.0%) on five occasions with, in random sequence, bedtime (2200 h) administration of 1) no treatment, 2) a snack, 3) the snack plus the alpha-glucosidase inhibitor acarbose, 4) an uncooked cornstarch bar, or 5) the beta(2)-adrenergic agonist terbutaline. In the absence of a bedtime treatment, 27% of the measured nocturnal plasma glucose concentrations were less than 70 mg/dl (3.9 mmol/liter) in 12 patients; 16, 6, and 1% were less than 60, less than 50, and less than 40 mg/dl (3.3, 2.8, and 2.2 mmol/liter), respectively. Neither the snack (without or with acarbose) nor cornstarch raised the mean nadir nocturnal glucose concentration or reduced the number of low glucose levels or the number of patients with low levels. Terbutaline raised the mean nadir nocturnal glucose concentration (mean +/- se, 127 +/- 11 vs. 75 +/- 9 mg/dl; P < 0.001), eliminated glucose levels less than 50 mg/dl (P = 0.038), reduced levels less than 60 mg/dl (P = 0.005) to one, and reduced levels less than 70 mg/dl (P = 0.001) to five (four at 2215 h, one at 2230 h). However, it also raised glucose levels the following morning. Nocturnal hypoglycemia is common in aggressively treated type 1 diabetes. Bedtime administration of a conventional snack or of uncooked cornstarch does not prevent it. That of terbutaline prevents nocturnal hypoglycemia but causes hyperglycemia the following morning. The efficacy of a lower dose of terbutaline remains to be determined.

Nocturnal hypoglycaemia in type 1 diabetes?consequences and assessment

Hypoglycaemia is inevitable when striving for low HbA1c values. Nocturnal hypoglycaemia often occurs without symptoms, but results in diminished next day well-being and hypoglycaemia unawareness. Frequency of nocturnal hypoglycaemia was first assessed in research ward settings, but suffered from insufficient glucose sampling frequency. This may have resulted in overestimation of the duration of hypoglycaemic episodes. The advent of the first continuous glucose sensor, the needle-type MedtronicMiniMed Continuous Glucose Measurement System, revolutionized the assessment of glucose values. However, on scrutiny, the first version of this sensor showed a drift into the hypoglycaemic area and delayed recovery from hypoglycaemia. Using the microdialysis-based GlucoDay system, our group reported a lower frequency of nocturnal hypoglycaemia in type 1 diabetes patients using an insulin pump, than that expected from the existing literature. Today, more than 80 years after the introduction of insulin for the treatment of type 1 diabetes, the associated frequency of nocturnal hypoglycaemia still awaits its definitive assessment.

Sleep-related hypoglycemia-associated autonomic failure in type 1 diabetes: reduced awakening from sleep during hypoglycemia.

Given that iatrogenic hypoglycemia often occurs during the night in people with type 1 diabetes, we tested the hypothesis that physiological, and the resulting behavioral, defenses against developing hypoglycemia-already compromised by absent glucagon and attenuated epinephrine and neurogenic symptom responses-are further compromised during sleep in type 1 diabetes. To do so, we studied eight adult patients with uncomplicated type 1 diabetes and eight matched nondiabetic control subjects with hyperinsulinemic stepped hypoglycemic clamps (glucose steps of approximately 85, 75, 65, 55, and 45 mg/dl) in the morning (0730-1230) while awake and at night (2100-0200) while awake throughout and while asleep from 0000 to 0200 in random sequence. Plasma epinephrine (P = 0.0010), perhaps norepinephrine (P = 0.0838), and pancreatic polypeptide (P = 0.0034) responses to hypoglycemia were reduced during sleep in diabetic subjects (the final awake versus asleep values were 240 +/- 86 and 85 +/- 47, 205 +/- 24 and 148 +/- 17, and 197 +/- 45 and 118 +/- 31 pg/ml, respectively), but not in the control subjects. The diabetic subjects exhibited markedly reduced awakening from sleep during hypoglycemia. Sleep efficiency (percent time asleep) was 77 +/- 18% in the diabetic subjects, but only 26 +/- 8% (P = 0.0109) in the control subjects late in the 45-mg/dl hypoglycemic steps. We conclude that autonomic responses to hypoglycemia are reduced during sleep in type 1 diabetes, and that, probably because of their reduced sympathoadrenal responses, patients with type 1 diabetes are substantially less likely to be awakened by hypoglycemia. Thus both physiological and behavioral defenses are further compromised during sleep. This sleep-related hypoglycemia-associated autonomic failure, in the context of imperfect insulin replacement, likely explains the high frequency of nocturnal hypoglycemia in type 1 diabetes.