Incidence Of Nocturnal Hypoglycemia Research Articles

Strengths and Challenges of Closed-Loop Insulin Delivery During Exercise in People With Type 1 Diabetes: Potential Future Directions.

Exercise has many physical and psychological benefits and is recommended for people with type 1 diabetes; however, there are many barriers to exercise, including glycemic instability and fear of hypoglycemia. Closed-loop (CL) systems have shown benefit in the overall glycemic management of type 1 diabetes, including improving HbA1c levels and reducing the incidence of nocturnal hypoglycemia; however, these systems are challenged by the rapidly changing insulin needs with exercise. This commentary focuses on the principles, strengths, and challenges of CL in the management of exercise, and discusses potential approaches, including the use of additional physiological signals, to address their shortcomings in the pursuit of fully automated CL systems.

Nocturnal Hypoglycemia Associated with Bedtime Administration of Premixed Insulin Preparations in Hospitalized Patients.

Patients with diabetes mellitus for whom premixed insulin preparations (PMIPs) are ordered in the hospital setting may be at risk of hypoglycemia if the PMIP is incorrectly administered at bedtime (instead of suppertime). The primary objective was to determine, retrospectively, the incidence of bedtime administration of PMIPs at a tertiary teaching hospital. The secondary objective was to investigate whether bedtime administration of PMIPs led to an increase in nocturnal hypoglycemia. Inpatient PMIP orders for the period April 1, 2013, to March 31, 2017, were extracted from the pharmacy information system of the Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia. Two hundred randomly selected inpatient admissions were audited, and instances of PMIP administration after 2000 (8 pm) were recorded. Data from an additional random sample of inpatient admissions, from January 1, 2016, to December 31, 2017, were reviewed to determine whether bedtime administration of PMIPs was associated with increased incidence of nocturnal hypoglycemia, relative to suppertime administration. In the randomly selected sample of 200 inpatient admissions, a PMIP was administered at bedtime at least once during 47 admissions (24%). In the additional sample of 123 inpatient admissions during which a PMIP had been administered, the mean nocturnal hypoglycemia rate was 4.15% for suppertime administration and 14.85% for bedtime administration (p = 0.13). For a substantial proportion of patients, PMIPs were inappropriately ordered and administered at bedtime in this hospital setting and may have been associated with nocturnal hypoglycemic events. Recommendations to reduce this practice include ongoing education and a review of preprinted order sets.

Insulin Glargine U100 Improved Glycemic Control and Reduced Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease Stages 3 and 4

PurposeGlycemic control in patients with chronic kidney disease (CKD) is particularly hard to achieve because of a slower insulin degradation by the kidney. It might modify the long-acting insulin analogue pharmacokinetics, increasing its time–action and the risk of hypoglycemia. However, because this insulin has no peak action, it might be a more tolerable approach to patients with CKD. This hypothesis remains to be tested, because no study has thus far examined the efficacy and safety profile of long-acting basal analogues in patients with significant loss of renal function. The purpose of this study was to compare the glycemic response to treatment with glargine U100 or neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus (T2DM) and CKD stages 3 and 4. MethodsThirty-four patients were randomly assigned to glargine U100 or NPH insulin after a 2-way crossover open-label design. The primary end point was the difference in glycosylated hemoglobin (HbA1c) and in the number of hypoglycemic events between weeks 1 and 24, whereas secondary end points included changes in glycemic patterns, weight and body mass index, and total daily dose of insulin. HbA1c was determined by ion-exchange HPLC, and hypoglycemia was defined as glucose concentration of 54 mg/dL (3.0 mmol/L) detected by self-monitoring of plasma glucose or continuous glucose monitoring. FindingsAfter 24 weeks, mean HbA1c decreased on glargine U100 treatment (−0.91%; P < 0.001), but this benefit was not observed for NPH (0.23%; P = 0.93). Moreover, incidence of nocturnal hypoglycemia was 3 times lower with glargine than with NPH insulin (P = 0.047). ImplicationsOur results found that insulin glargine U100 could be effective, once it improved glycemic control, reducing HbA1c with fewer nocturnal hypoglycemia episodes compared with NPH insulin in this population. These clinical benefits justify the use of basal insulin analogues, despite their high cost to treat patients with T2DM and CKD stages 3 and 4. Clinical Trials identifier: NCT02451917.

Predicting Nocturnal Hypoglycemia with Measures of Physical Activity Intensity in Adolescent Athletes with Type 1 Diabetes.

For someone managing type 1 diabetes, understanding their body's glucose response to physical activity could aid in effectively addressing nocturnal hypoglycemia. The purpose of this investigation was to examine the acute temporal associations between blood glucose and measures of moderate-vigorous physical activity (MVPA) through an accelerometer. Ten adolescent athletes with type 1 diabetes wore an accelerometer and continuous glucose monitor (CGM) consecutively for a minimum of 2 weeks. Physical activity was analyzed according to intensity indicating time spent in light, moderate, and vigorous intensities. Hypoglycemic episodes were defined as two successive CGM readings <70 mg/dL, at 5-min intervals, with an episode ending with at least two CGM readings >70 mg/dL. Incidence of nocturnal hypoglycemia occurred during 29% of the nights measured with an average duration of 52.33 ± 41.04 min. When combining total minutes of moderate and vigorous intensities a significant difference was observed between combined MVPA and number of nocturnal hypoglycemic episodes (62.92 min vs. 49 episodes, P = 0.02). Moderate intensity activity alone was not significant in predicting hypoglycemic events or duration. Vigorous intensity physical activity was a significant predictor of nocturnal hypoglycemia after controlling for sedentary and light intensity minutes, age, and gender (β = 0.21, P = 0.01) with an average time of 26 min of vigorous intensity. Engaging in vigorous intensity physical activity increased the risk of prolonged nocturnal hypoglycemia in adolescent athletes with type 1 diabetes. Incorporating accelerometers into patient care could prove beneficial when making further recommendations for athletes.

Effectiveness of insulin glargine U-300 versus insulin glargine U-100 on nocturnal hypoglycemia and glycemic control in type 1 and type 2 diabetes: a systematic review and meta-analysis.

To assess the effectiveness of insulin glargine 300 ui/ml (Gla-300) compared with insulin glargine 100 ui/ml (Gla-100) on reducing nocturnal hypoglycemia and improving glycemic control in type 1 and type 2 diabetes patients. We systematically searched in Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials until July 4th, 2018. This study was registered with PROSPERO (CRD42017080134). We included randomized clinical trials comparing Gla-300 versus Gla-100 reporting the rate ratio or number of events of nocturnal hypoglycemia and HbA1c levels percentage or mmol/mol-1. The main outcome was the incidence rate ratio (RR) of nocturnal hypoglycemia events. The heterogeneity of results across studies was assessed using the I2 statistic. Fixed- and random-effect models were used to estimate pooled RRs. Nine studies were included in the meta-analysis, including 3977 adult patients. Compared with Gla-100, the use of Gla-300 reduced confirmed nocturnal hypoglycemia [RR = 0.81 (0.69, 0.95)] and clinically significant nocturnal hypoglycemia [RR = 0.75 (0.63, 0.91)]. Reductions in clinically significant nocturnal hypoglycemia events [RR = 0.64 (0.42, 0.97)] in type 1 diabetes patients were found. A small decrease in HbA1c levels in favor of Gla-300 in the pooled sample was identified [ES = -0.08 (95% CI -0.14, -0.01)]. The best current evidence indicates that Gla-300 reduces the incidence of nocturnal hypoglycemia with slight improvements in glycemic control compared with Gla-100 in both type 1 and type 2 diabetes adult patients.

Effect of moderate exercise for 30 min at 30 min versus 60 min after dinner on glycemic control in patients with type 2 diabetes: a randomized, crossover, self-controlled study

To compare the effectiveness of moderate exercise for 30 min at 30 min and 60 min after dinner on glycemic control in patients with type 2 diabetes. This randomized, crossover, self-controlled pilot study was conducted in 15 inactive patients with type 2 diabetes without serious complications or use of exogenous insulin. The participants completed two randomly ordered exercise protocols (brisk walking for 30 min at 30 min or 60 min after dinner on the exercise day) spaced 1 week apart. All the exercise was performed while maintaining a heart rate reserve of 40%. The interstitial glucose level was monitored using a continuous glucose monitor (CGM) for all the participants, who maintained a standardized diet with routine medications. The 2-h postprandial mean glucose, peak glucose, and glucose area under the curve (AUC) were measured. The mean amplitude of glycemic excursions (MAGE) and other plasma glucose fluctuation parameters in 12 h after dinner, including the mean blood glucose (MBG) and the coefficient variation (CV) of glucose, were also calculated. The incidence of nocturnal hypoglycemia was recorded in all the participants. The participants had a mean age of 46±11 years with a mean BMI of 25.8±3.1 kg/m2 and a mean HbA1c of 7.7%. No significant differences were found between postprandial 30 min exercise group and postprandial 60 min exercise group in terms of 2-h postprandial mean glucose, peak glucose, glucose AUC, or in MBG, CV and MAGE during the 12-h period after dinner. No nocturnal hypoglycemia occurred in the participants after exercise at 30 or 60 min after dinner. However, significant reductions in the 2-h postprandial glucose levels were detected after exercise at 60 min after dinner as compared to exercise at 30 min. The timing (30 min vs 60 min after dinner) of moderate exercises for 30 min does not produce significant difference in the improvement of postprandial hyperglycemia in type 2 diabetic patients, and both exercise protocols are safe without a potential risk of hypoglycemia. Nevertheless, exercise at 60 min after dinner can be more effective to lower 2-h postprandial glucose, while exercise at 30 min after dinner might be safer for patients with a high risk of hypoglycemia.

Glycaemic control, hypoglycaemia, and weight change with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Japanese adults with type 2 diabetes: A 12‐month comparison by concomitant sulphonylurea and/or glinide use

AimTo explore if clinical effects and hypoglycaemia risks associated with insulin glargine 300 U/mL (Gla‐300) and 100 U/mL (Gla‐100) differed by sulphonylurea and/or glinide (SU/G) treatment.MethodsA post hoc subgroup analysis of 12‐month treatment data from the EDITION Japan 2 trial, a randomized, open‐label, phase 3 study of Japanese people with type 2 diabetes receiving once‐daily Gla‐300/Gla‐100 + oral antihyperglycaemic drugs. Participants previously receiving SU/G (+SU/G) were compared with those not taking SU/G (‐SU/G). Endpoints included HbA1c, hypoglycaemia and body weight.ResultsFor +SU/G (n = 152, 63%), HbA1c was reduced from baseline to month 12 for Gla‐300 (8.1% to 7.6%) and Gla‐100 (8.2% to 7.8%). For ‐SU/G (n = 89, 37%), reductions were 7.8% to 7.4%, and 7.9% to 7.5% for Gla‐300 and Gla‐100, respectively. A lower annualized rate of hypoglycaemia with Gla‐300 versus Gla‐100 was observed at night (00:00–05:59 hours; p = 0.0001) and any time of day (24 hour; p = 0.0015). Irrespective of the insulin used, the incidence and rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia appeared higher in +SU/G versus ‐SU/G; overall, a reduced incidence of nocturnal hypoglycaemia, and rate of hypoglycaemia at any time, was observed in ‐SU/G versus +SU/G. In the ‐SU/G subgroup, body weight gain differences were observed between Gla‐300 and Gla‐100 (p < 0.0001).ConclusionsParticipants with prior and continued SU/G use had similar therapeutic responses with basal insulin but greater risk of hypoglycaemia than those not using SU/G; hypoglycaemia risk was lower with Gla‐300 than Gla‐100 in both subgroups.

Comparative Benefits and Harms of Basal Insulin Analogues for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

Basal insulin analogues aim for protracted glycemic control with minimal adverse effects. To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM). Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books. Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level <7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues. Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence. Thirty-nine trials (26195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300. Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency. Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300). None. (PROSPERO: CRD42016037055).

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

IntroductionAlthough reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported.MethodsForty patients with type 2 diabetes who were admitted for glycemic control with basal–bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100–120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge.ResultsIn the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033).ConclusionIn type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100.Trial RegistrationUMIN clinical trials registry (UMIN000023360).

The risks of nocturnal hypoglycaemia in insulin-treated diabetes.

Over half of all episodes of severe hypoglycaemia (requiring external help) occur during sleep, but nocturnal hypoglycaemia is often asymptomatic and unrecognised. The precise incidence of nocturnal hypoglycaemia is difficult to determine with no agreed definition, but continuous glucose monitoring has shown that it occurs frequently in people taking insulin. Attenuation of the counter-regulatory responses to hypoglycaemia during sleep may explain why some episodes are undetected and more prolonged, and modifies cardiovascular responses. The morbidity and mortality associated with nocturnal hypoglycaemia is probably much greater than realised, causing seizures, coma and cardiovascular events and affecting quality of life, mood and work performance the following day. It may induce impaired awareness of hypoglycaemia. Cardiac arrhythmias that occur during nocturnal hypoglycaemia include bradycardia and ectopics that may provoke dangerous arrhythmias. Treatment strategies are discussed that may help to minimise the frequency of nocturnal hypoglycaemia.

The Effects of Evening Exercise Mode on Nocturnal Hypoglycemia During an Adult Diabetes Training Camp

Exercise is a cornerstone for diabetes management. Still, glycemic control has proven difficulty in exercisers with type 1 diabetes. While light to moderate aerobic and relaxation style exercise, like Yoga, frequently show reductions in glucose levels, anaerobic exercise can increase glucose due to its adrenergic effects. These responses may ensue both during and after the bout making treatment difficult and increasing risk of hypoglycemia, often occurring overnight. PURPOSE: To examine the effects of different exercise modes (Hatha Yoga versus Resistance Training) on the incidence of nocturnal hypoglycemia in adults with diabetes participating in a week long, high volume exercise training camp. METHODS: Adults with diabetes attending the 2015 Diabetes Training Camp™ were recruited to volunteer in this study. Participants were randomized to 1 of 3 groups: 1) Hatha Yoga (Y); Resistance Training Circuit (RT); or Non- exercise control (C). Each intervention group performed 45 minutes of evening exercise for 3 consecutive days. Data were collected through either electronic uploading using continuous glucose monitoring or self-reported monitoring. RESULTS: Twelve participants provided complete data to be analyzed (6 RT, 5 Y and 1 C). Demographics involved a mean age of 49.2±13 years; 83% female; 92% Caucasian; BMI=26.5±3.8 kg/m2; estimated VO2peak=36±7.4 ml/kg/min. Also, 75% of the adults were current exercisers with a mean of 4±2 days of hypoglycemic events per week. No significant differences were found between the groups. Overall, 41% of the study participants experienced at least one nocturnal hypoglycemic event (1 of 6 in RT; 3 of 5 Y; and 1 of 1 C) during the 3 day study. Those who participated in either the Y or C group were more likely to experience a nocturnal hypoglycemic event compared to the Resistance Training group (p= .068). Additionally, 40% of the Y group experienced nocturnal hypoglycemia on at least 2 of the 3 nights compared to only 16% in the RT group (p=.80). CONCLUSION: Performing RT in the evening, following a high volume of various exercise activities throughout the day, may reduce the incidence of nocturnal hypoglycemia. Future studies should examine additional exercise strategies, with larger samples, to reduce the barriers of hypoglycemia in adults exercising with diabetes.

A low-glycemic index meal and bedtime snack prevents postprandial hyperglycemia and associated rises in inflammatory markers, providing protection from early but not late nocturnal hypoglycemia following evening exercise in type 1 diabetes.

To examine the influence of the glycemic index (GI) of foods consumed after evening exercise on postprandial glycemia, metabolic and inflammatory markers, and nocturnal glycemic control in type 1 diabetes. On two evenings (∼1700 h), 10 male patients (27 ± 5 years of age, HbA1c 6.7 ± 0.7% [49.9 ± 8.1 mmol/mol]) were administered a 25% rapid-acting insulin dose with a carbohydrate bolus 60 min before 45 min of treadmill running. At 60 min postexercise, patients were administered a 50% rapid-acting insulin dose with one of two isoenergetic meals (1.0 g carbohdyrate/kg body mass [BM]) matched for macronutrient content but of either low GI (LGI) or high GI (HGI). At 180 min postmeal, the LGI group ingested an LGI snack and the HGI group an HGI snack (0.4 g carbohdyrate/kg BM) before returning home (∼2300 h). Interval samples were analyzed for blood glucose and lactate; plasma glucagon, epinephrine, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); and serum insulin, cortisol, nonesterified fatty acid, and β-hydroxybutyrate concentrations. Interstitial glucose was recorded for 20 h postlaboratory attendance through continuous glucose monitoring. Following the postexercise meal, an HGI snack induced hyperglycemia in all patients (mean ± SD glucose 13.5 ± 3.3 mmol/L) and marked increases in TNF-α and IL-6, whereas relative euglycemia was maintained with an LGI snack (7.7 ± 2.5 mmol/L, P < 0.001) without inflammatory cytokine elevation. Both meal types protected all patients from early hypoglycemia. Overnight glycemia was comparable, with a similar incidence of nocturnal hypoglycemia (n = 5 for both HGI and LGI). Consuming LGI food with a reduced rapid-acting insulin dose following evening exercise prevents postprandial hyperglycemia and inflammation and provides hypoglycemia protection for ∼8 h postexercise; however, the risk of late nocturnal hypoglycemia remains.

A new generation ultra-long-acting insulin analogue-insulin degludec

Patients with diabetes usually require long-term insulin medication.Hypoglycemia,weight gain and cancer risk induced by insulin medication are the factors that should be considered in the selection of insulin medication protocols.Being a basal insulin,insulin degludec is a brand-new ultra-long-acting insulin analogue.With unique advantages of stable and slow release,sustained acting time,minor absorption variability,low incidence of hypoglycemia,flexible dosage,good control of high blood glucose and low incidence of nocturnal hypoglycemia,insulin degludec offers a new choice for insulin therapy of diabetes patients.

A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations

Insulin analogues have been engineered to enhance desired molecular properties without altering immunogenicity. The majority of insulin pharmacology studies are conducted in healthy volunteers and patients with type 1 diabetes. At present, there are more patients with type 2 than type 1 diabetes receiving insulin treatment. As the responsibility for initiating insulin therapy in these patients continues to shift to primary care, it will be important for general practitioners to understand the different pharmacological properties of insulin preparations in patients with type 2 diabetes, so that treatment can be adapted to meet patients’ physiological and lifestyle requirements. The purpose of this review is to summarize pharmacological studies of insulin analogues in patients with type 2 diabetes. Faster onset of action of rapid acting insulin analogues has improved postprandial glycaemic control. Biphasic insulin analogues are associated with a lower incidence of nocturnal hypoglycaemia compared with human biphasic preparations and allow for intensification from once to twice or thrice daily dosing. More predictable glycaemic-lowering profiles of the insulin analogues have also led to reductions in nocturnal hypoglycaemia, particularly comparing long-acting insulin analogues with protaminated human insulin. Enhancing insulin self-association and reversible binding with albumin has led to further reductions in variability. However, improvements can still be made. Effective once daily clinical dosing of long-acting insulin analogues is not possible in all patients. In addition, the protaminated component of biphasic insulin analogues do not provide the duration of action or profile for physiological basal insulin replacement and neither insulin glargine nor insulin detemir are suitable for mixing with other insulin analogues as this would substantially alter their pharmacokinetic properties. Enhancing the pharmacological predictability and extending the duration of action could simplify insulin titration and further reduce the incidence of hypoglycaemia.

28‐week, randomized, multicenter, open‐label, parallel‐group phase III trial to investigate the efficacy and safety of biphasic insulin aspart 70 thrice‐daily injections vs twice‐daily injections of biphasic insulin aspart 30 in patients with type 2 diabetes

Aims/Introduction: An insulin analogue formulation with a 7:3 ratio of rapid-acting and intermediate-acting fractions, biphasic insulin aspart 70 (BIAsp70) was developed to supplement basal insulin between meals and mimic the physiological pattern of postprandial insulin secretion. We carried out a randomized, open-label study to compare the efficacy and safety profiles of BIAsp70 and an insulin analogue formulation with a 3:7 ratio of rapid-acting and intermediate-acting fractions (BIAsp30) in type 2 diabetes mellitus patients. Patients were randomized and received either thrice-daily BIAsp70 (n = 145) or twice-daily BIAsp30 (n = 144) for 28 weeks. The primary end-point was glycated hemoglobin (HbA1c) after 16 weeks of treatment. Non-inferiority of BIAsp70 vs BIAsp30 was confirmed and superiority was established with a between-group difference (BIAsp70-BIAsp30) in HbA1c after 16 weeks of treatment of -0.35% (95% CI: -0.51 to -0.19; P < 0.0001 for superiority). The mean postprandial glucose increment (19.96 vs 54.35 mg/dL; P < 0.0001) and M-value (12.99 vs 17.94; P < 0.0001) at 16 weeks were smaller in the BIAsp70 group than in the BIAsp30 group, and were maintained at 28 weeks. Pre-breakfast glucose (157.9 vs 140.7 mg/dL), total insulin dose (46.8 vs 38.1 U/day) and weight gain (+1.94 vs 1.23 kg) at week 28 were greater in the BIAsp70 group. Incidence of nocturnal hypoglycemia was significantly lower with BIAsp70 vs BIAsp30 (1.23 vs 3.21 events/subject year; P = 0.0002) at week 28. Thrice-daily BIAsp70 was superior to twice-daily BIAsp30 in terms of HbA1c change, with less variation in daytime plasma glucose profiles. BIAsp70 was well tolerated, with a lower incidence of nocturnal hypoglycemia vs BIAsp30. This trial was registered with ClinicalTrial.gov (no. NCT00318786). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00015.x, 2010).

Evaluation of nocturnal hypoglycemia in patients with type 2 diabetes via continuous glucose monitoring system

The variation of blood glucose in 1 147 patients with type 2 diabetes mellitus was monitored by continuous glucose monitoring system(CGMS). The results showed that the peak hours of nocturnal hypoglycemia occurred during 22 : 00-2 : 00. The incidence of nocturnal hypoglycemia was negatively correlated with mean blood glucose and blood glucose at three hours after supper. The probability of hypoglycemia was up to 50% when blood glucose level had been as low as 4. 7 mmol/L at 3 h after supper. Key words: Continuous glucose monitoring system; Diabetes mellitus,type 2; Hypoglycemia

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.

Prolonged Nocturnal Hypoglycemia Is Common During 12 Months of Continuous Glucose Monitoring in Children and Adults With Type 1 Diabetes

OBJECTIVETo characterize the amount of nocturnal hypoglycemia and evaluate factors associated with nocturnal hypoglycemia assessed with continuous glucose monitoring (CGM) in adults and children with type 1 diabetes who participated in the Juvenile Diabetes Research Foundation CGM randomized clinical trial.RESEARCH DESIGN AND METHODSThe analysis included 36,467 nights with ≥4 h of CGM glucose readings between 12 midnight and 6:00 a.m. from 176 subjects assigned to the CGM group of the trial. The percentage of nights in which hypoglycemia occurred (two consecutive CGM readings ≤60 mg/dl in 20 min) was computed for each subject. Associations with baseline characteristics and clinical factors were evaluated using a multivariate regression model.RESULTSHypoglycemic events occurred during 8.5% of nights, with the median percentage of nights with hypoglycemia per subject being 7.4% (interquartile range 3.7–12.1%). The duration of hypoglycemia was ≥2 h on 23% of nights with hypoglycemia. In a multivariate model, a higher incidence of nocturnal hypoglycemia was associated with 1) lower baseline A1C levels (P < 0.001) and 2) the occurrence of hypoglycemia on one or more nights during baseline blinded CGM (P < 0.001). The hypoglycemia frequency was not associated with age or with insulin modality (pump versus multiple daily injections).CONCLUSIONSNocturnal hypoglycemia is frequent and often prolonged in adults and children with type 1 diabetes. Patients with low A1C levels are at an increased risk for its occurrence. One week of blinded CGM can identify patients who are at greater risk for nocturnal hypoglycemia.

Exenatide compared with long‐acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long‐Acting insulin (HEELA) study

Aim: The Helping Evaluate Exenatide in overweight patients with diabetes compared with Long-Acting insulin (HEELA) study was designed to examine whether the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, could improve HbA1c (≤7.4%) with minimal weight gain (≤1 kg) compared with insulin glargine.Methods: Patients [body mass index (BMI) >27 kg/m2] with elevated cardiovascular risk and type 2 diabetes inadequately controlled on two or three oral antidiabetes drugs (OADs) were randomized to add-on exenatide 5–10 μg b.i.d. (n = 118) or insulin glargine o.d. (titrated to target fasting plasma glucose ≤5.6 mmol/l; n = 117) for 26 weeks.Results: The study population had baseline mean (s.d.) age of 56.5 (9.1) years and BMI of 34.1 (5.3) kg/m2, and 58.5% of patients were taking two OADs. Mean baseline HbA1c was 8.65 (0.68)% in the exenatide group and 8.48 (0.66)% in the insulin glargine group. The proportions of patients achieving the composite endpoint of HbA1c ≤7.4% with weight gain ≤1 kg were 53.4% for the exenatide group and 19.8% for the insulin glargine group (p < 0.001 for exenatide vs. insulin glargine). Exenatide and insulin glargine did not demonstrate a significant difference in HbA1c improvements [least square (LS) mean [s.e.m.]: −1.25 [0.09]% and −1.26 [0.09]% respectively; p = 0.924], but had divergent effects on body weight (−2.73 [0.31] vs. +2.98 [0.31] kg respectively, p < 0.001) after 26 weeks. There were more treatment-related adverse events with exenatide but a lower incidence of nocturnal hypoglycaemia, with no differences in overall or severe hypoglycaemia.Conclusions: Additional treatment with exenatide resulted in significantly more overweight and obese patients with an elevated cardiovascular risk and type 2 diabetes achieving better glycaemic control with minimal weight gain compared with insulin glargine.

Postprandial glycemic control using insulin aspart with NPH in inadequately controlled diabetics

To compare the efficacy and safety of insulin aspart (IAsp) and human insulin (HI) when applied as meal-time insulin with neutral protamine Hagedorn insulin (NPH) at bedtime in diabetics. A total of 220 Chinese subjects with type 1 or type 2 diabetes from 5 different hospitals were randomized by a ratio of 1:1 into two groups accepting IAsp or HI combined with NPH respectively. The main endpoints were assessed by fasting plasma glucose (FPG), 2 hour postprandial plasma glucose (2 h PPG), HbAlc and hypoglycemia. A greater reduction in mean 2 h PPG was achieved in the IAsp group [(14.6 +/- 5.3) mmol/L] as compared with the HI group [(8.4 +/- 4.1) mmol/L] (P < 0.01, adjusted for baseline value, center effect and diabetes type). Significantly more IAsp-treated subjects reached the 2 h PPG target (50.0% vs 25.5%, P < 0.01). HbA1c was reduced more in IAsp/NPH group [(9.3 +/- 1.4)% vs (7.7 +/- 1.3)%] than in HI/NPH group [(9.2 +/- 1.2)% vs (7.7 +/- 1.2)%]. HbA1c target was reached by 24.5% (IAsp) vs 14.5% (HI) of subjects (P < 0.05). No major hypoglycemia or serious adverse events were observed for the IAsp group. Lower incidence of nocturnal hypoglycemia (IAsp/NPH: 3% vs HI/NPH: 4%) was reported in the IAsp group. Average daily insulin doses were 0.60/0.23 (IAsp/NPH) and 0.65/0.24 (HI/NPH) IU/kg respectively. Treatment of IAsp in basal-bolus therapy in combination with NPH provides a superior postprandial glucose control and allows more subjects to reach the glycemic target without elevating the nocturnal hypoglycemic risk or adverse events.