Hypoglycemia during prolonged exercise in normal men. Health-related quality of life and treatment satisfaction in the Sensor-Augmented Pump Therapy for A1C Reduction 3 (STAR 3) trial. Randomized Controlled Clinical Trial of Blood Glucose Awareness Training (BGAT III) in Switzerland and Germany An Integrated Multivariable Artificial Pancreas Control System Continuous glucose monitoring reveals delayed nocturnal hypoglycemia after intermittent high-intensity exercise in nontrained patients with type 1 diabetes. Glucose or intermittent high-intensity exercise in glargine/glulisine users with T1DM. Reduced Hypoglycemia and Increased Time in Target Using Closed-Loop Insulin Delivery During Nights With or Without Antecedent Afternoon Exercise in Type 1 Diabetes The blood glucose lowering effects of exercise and glibenclamide in patients with type 2 diabetes mellitus. Severe sulfonylurea-induced hypoglycemia: a problem of uncritical prescription and deficiencies of diabetes care in geriatric patients Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion. Carbohydrate requirement and insulin concentration during moderate exercise in type 1 diabetic patients. Psychosocial correlates of continuous glucose monitoring use in youth and adults with type 1 diabetes and parents of youth. A Randomized Clinical Trial to Assess the Efficacy and Safety of Real-Time Continuous Glucose Monitoring in the Management of Type 1 Diabetes in Young Children Aged 4 to <10 Years Effects of 12 weeks combined aerobic and resistance exercise on heart rate variability in type 2 diabetes mellitus patients [Benefits of a home-based physical exercise program in elderly subjects with type 2 diabetes mellitus]. Administration of Neutral Protamine Hagedorn Insulin at Bedtime versus with Dinner in Type 1 Diabetes Mellitus To Avoid Nocturnal Hypoglycemia and Improve Control Glucagon-like peptide-1 receptor agonists as add-on therapy to basal insulin in patients with type 2 diabetes: a systematic review Closing the loop overnight at home setting: psychosocial impact for adolescents with type 1 diabetes and their parents Severe Hypoglycemia Requiring Medical Intervention in a Large Cohort of Adults With Diabetes Receiving Care in U.S. Integrated Health Care Delivery Systems: 2005–2011 A pilot program for physical exercise promotion in adults with type 1 diabetes: the PEP-1 program. Hypoglycemia anticipation, awareness and treatment training (HAATT) reduces occurrence of severe hypoglycemia among adults with type 1 diabetes mellitus Effects of a Fixed Mixture of 25% Insulin Lispro and 75% NPL on Plasma Glucose during and after Moderate Physical Exercise in Patients with Type 2 Diabetes Glycemic Control in Medical Inpatients with Type 2 Diabetes Mellitus Receiving Sliding Scale Insulin Regimens versus Routine Diabetes Medications: A Multicenter Randomized Controlled Trial
Hypoglycemia ( blood glucose less than 45 mg per deciliter [ less than 2.5 mmol per liter ] ) occurred in seven of 19 healthy men who exercised to exhaustion on a cycle ergometer at 60 to 65 per cent of maximal aerobic power . The hypoglycemic subjects exercised for 15 to 70 minutes despite blood glucose levels of 25 to 48 mg per deciliter ( 1.4 to 2.7 mmol per liter ) , and their exhaustion time ( mean + /- S.E.M. , 142 + /- 15 minutes ) was not significantly different from that of the euglycemic group ( 165 + /- 11 ) . Plasma epinephrine was inversely related to blood glucose ( P less than 0.01 ) and was three times higher in the hypoglycemic subjects ( P less than 0.05 ) . Glucose ingestion ( 40 or 80 g per hour ) prevented the hypoglycemia and result ed in a smaller rise in plasma epinephrine but did not alter perceived exertion or consistently delay exhaustion . We conclude that hypoglycemia occurs in normal subjects during prolonged exercise and results in an exaggerated rise in plasma epinephrine . However , hypoglycemia fails to effect endurance , and its prevention does not consistently delay exhaustion OBJECTIVE This study assessed health-related quality of life ( HRQOL ) and treatment satisfaction in sensor-augmented pump therapy ( SAPT ) compared with optimal conventional therapy-multiple daily injection ( MDI ) therapy with self-monitoring of blood glucose (SMBG)-in  adults and children with type 1 diabetes and children 's caregivers . Patient acceptance of new therapies is essential to their adoption and effective use . RESEARCH DESIGN AND METHODS STAR 3 , a r and omized 12-month clinical trial , compared SAPT with MDI+SMBG in 485 adult and pediatric patients . Within- and between-treatment arm changes in generic HRQOL , diabetes-specific HRQOL ( fear of hypoglycemia ) , and treatment satisfaction were assessed ( significance criterion P<0.01 ) . RESULTS In adults , children , and caregivers , there were no significant between-arm changes in generic HRQOL : SF-36 Physical Component Summary and Mental Component Summary scores in adults and the PedsQL Physical Health Summary and Psychosocial Health Summary scores in children or caregivers . Diabetes-specific HRQOL ( Hypoglycemia Fear Survey Worry and Behavior subscale scores ) improved more in SAPT than in MDI adults . Hypoglycemia Behavior scores improved more in SAPT caregivers . Key treatment satisfaction measures ( Insulin Delivery System Rating Question naire measures of Convenience , Efficacy , and Overall Preference ) improved more in SAPT adults , children , and caregivers ( all P<0.001 ) ; all exceeded the criterion for minimal detectable difference . CONCLUSIONS In the first-ever large-scale study of SAPT compared with optimal conventional therapy , SAPT had significant advantages for hypoglycemia fear in adults and caregivers and for treatment satisfaction in adults , children , and caregivers Although both diabetes and the efficacy of medical management are international issues , psycho-educational interventions might be culturally bound . Blood Glucose Awareness Training ( BGAT ) is a psycho-educational program for patients with type 1 diabetes mellitus . It is focused on improving recognition and management of extreme blood glucose levels , and is the best documented American psycho-educational program for this purpose . A r and omized controlled clinical trial of BGAT 's long-term benefits in a non-American setting has been lacking . One hundred and eleven adults with type 1 diabetes mellitus from Switzerl and and Germany participated . After a 6 months baseline assessment , subjects were r and omly assigned to receive either 2 months of BGAT ( n = 56 ) or a physician-guided self-help control intervention ( n = 55 ) . BGAT  improved recognition of low ( p = 0.008 ) , high ( p = .03 ) , and overall blood glucose ( p = 0.001 ) , and reduced frequency of severe hypoglycemia ( p = 0.04 ) , without compromising metabolic control .  BGAT reduced both the external locus of control ( p < 0.02 ) and fear of hypoglycemia ( p < 0.02 ) . BGAT was efficacious in reducing adverse clinical events and achieving clinical ly desirable goals in a European , as well as American setting Objective : The objective was to develop a closed-loop ( CL ) artificial pancreas ( AP ) control system that uses continuous measurements of glucose concentration and physiological variables , integrated with a hypoglycemia early alarm module to regulate glucose concentration and prevent hypoglycemia . Material s and Methods : Eleven open-loop ( OL ) and 9 CL experiments were performed . A multivariable adaptive artificial pancreas ( MAAP ) system was used for the first 6 CL experiments . An integrated multivariable adaptive artificial pancreas ( IMAAP ) system consisting of MAAP augmented with a hypoglycemia early alarm system was used during the last 3 CL experiments . Glucose values and physical activity information were measured and transferred to the controller every 10 minutes and insulin suggestions were entered to the pump manually . All experiments were design ed to be close to real-life conditions . Results : Severe hypoglycemic episodes were seen several times during the OL experiments . With the MAAP system , the occurrence of severe hypoglycemia was decreased significantly ( P < .01 ) . No hypoglycemia was seen with the IMAAP system . There was also a significant difference ( P < .01 ) between OL and CL experiments with regard to percentage of glucose concentration ( 54 % vs 58 % ) that remained within target range ( 70 - 180 mg/dl ) . Conclusions : Integration of an adaptive control and hypoglycemia early alarm system was able to keep glucose concentration values in target range in patients with type 1 diabetes . Postpr and ial hypoglycemia and exercise-induced hypoglycemia did not occur when this system was used . Physical activity information improved estimation of the blood glucose concentration and effectiveness of the control system OBJECTIVE Exercise is a cornerstone of diabetes therapy in type 1 diabetes mellitus ( DMT1 ) patients . The type of exercise is important in determining the propensity to hypoglycemia . We assessed , by continuous glucose monitoring ( CGM ) , the glucose profiles during and in the following 20h after a session of two different types of exercise . RESEARCH DESIGN AND METHODS Eight male volunteers with well-controlled DMT1 were studied . They underwent 30min of both intermittent high-intensity exercise ( IHE ) and moderate-intensity exercise ( MOD ) in r and om order . Expired air was recorded during exercise , while metabolic and hormonal determinations  were performed before and for 120 min after exercises . The CGM system and activity monitor were applied for the subsequent 20h . RESULTS Blood glucose level declined during both type of exercise . At 150 min following the start of exercise , plasma glucose content was slightly higher after IHE . No changes were observed in plasma insulin concentration . A significant increase of norepinephrine concentration was noticed during IHE . Between midnight and 6:00 a.m. the glucose levels were significantly lower after IHE than those observed after MOD ( area under the curve , 23.3 ± 3 vs. 16 ± 3 mg/dL/420 min [ P = 0.04 ] ; mean glycemia at 3 a.m. , 225 ± 31 vs. 147 ± 17 mg/dL [ P<0.05 ] ) . The number of hypoglycemic episodes after IHE was higher than that observed after MOD ( seven vs. two [ P<0.05 ] ) . CONCLUSIONS We demonstrate that ( 1 ) CGM is a useful approach in DMT1 patients who undergo an exercise program and ( 2 ) IHE is associated with delayed nocturnal hypoglycemia INTRODUCTION The effects of glargine/glulisine insulin regimen on exercise blood glucose ( BG ) and strategies to limit exercise-induced hypoglycemia are not well documented . Intermittent high-intensity exercise has been proposed to prevent hypoglycemia , but its effect in participants with type 1 diabetes using glargine/glulisine  is unknown . METHODS The study used a repeated- measures design with three r and omly ordered exercise conditions . Eleven participants completed 60 min of moderate-intensity exercise  at 50 % VO(2peak ) for all conditions . These conditions varied as follows : participants ingested 0 g of glucose preexercise ( 0 G + MOD ) , 30 g of glucose preexercise ( 30 G + MOD ) , or 0 g of glucose preexercise but performed brief high-intensity intervals interspersed every 2 min ( 0 G + MOD/INT ) during exercise . If BG fell < 4 mmol·L(-1 ) , a 20 % dextrose solution was started to maintain BG between 4 and 5 mmol·L(-1 ) . RESULTS Consuming 30 g of glucose before exercise ( 30 G + MOD ) result ed in a higher preexercise BG ( 11.7 ± 2.7 mmol·L(-1 ) ) compared with 0 g of glucose before exercise ( 0 G + MOD , 7.8 ± 4.0 , and 0 G + MOD/INT , 9.2 ± 3.5mmol·L(-1 ) ) , P < 0.05 . A dextrose infusion was required in 7/11 , 4/11 , and 1/11 participants for 0 G + MOD , 0 G + MOD/INT , 30 G + MOD conditions , respectively , P < 0.02 . The duration and the quantity of dextrose infused were greatest in the 0 G + MOD condition , moderate in the to 0 G + MOD/INT condition , and minimal in the 30 G + MOD condition , P < 0.01 . CONCLUSION Our results suggest that both moderate-intensity exercise with a 30-g preexercise glucose beverage or interspersed with intermittent high-intensity sprints may be safe strategies to prevent hypoglycemia in glargine/glulisine users OBJECTIVE Afternoon exercise increases the risk of  nocturnal hypoglycemia ( NH ) in subjects with type 1 diabetes . We hypothesized that automated feedback-controlled closed-loop ( CL ) insulin delivery would be superior to open-loop ( OL ) control in preventing NH and maintaining a higher proportion of blood glucose levels within the target blood glucose range on nights with and without antecedent afternoon exercise . RESEARCH DESIGN AND METHODS Subjects completed two 48-h inpatient study periods in r and om order :  usual OL control and CL control using a proportional-integrative-derivative plus insulin feedback algorithm . Each admission included a sedentary day and an exercise day , with a st and ardized protocol of 60 min of brisk treadmill walking to 65–70 % maximum heart rate at 3:00 p.m. RESULTS Among 12 subjects ( age 12–26 years , A1C 7.4 ± 0.6 % ) , antecedent exercise increased the frequency of NH ( reference blood glucose < 60 mg/dL ) during OL control from six to eight events . In contrast , there was only one NH event each on nights with and without antecedent exercise during CL control ( P = 0.04 vs. OL nights ) . Overnight , the percentage of glucose values in target range was increased with CL control ( P < 0.0001 ) . Insulin delivery was lower between 10:00 p.m. and 2:00 a.m. on nights after exercise on CL versus OL , P = 0.008 . CONCLUSIONS CL insulin delivery provides an effective means to reduce the risk of NH while increasing the percentage of time spent in target range , regardless of activity level in the mid-afternoon . These data suggest that CL control could be of benefit to patients with type 1 diabetes even if it is limited to the overnight period Physical exercise is associated with a fall in serum insulin levels , whereas sulphonylurea administration increases insulin release . To date , the opposing effects of exercise and sulphonylurea administration have not been systematic ally studied in Type 2 diabetic patients , who are not infrequently treated with sulphonylureas . In this study nine patients with Type 2 diabetes mellitus were subjected to four treatments in r and om order on separate days : ( A ) endurance exercise after the administration of 3.5 mg glibenclamide ; ( B ) as A but given only 1.75 mg glibenclamide ; ( C ) as A but with placebo ; ( D ) rest and administration of 1.75 mg glibenclamide . Exercise and placebo result ed in only a small decrease in glycaemia . Rest and administration of 1.75 mg glibenclamide led to a moderate but steady fall in blood glucose concentrations . If glibenclamide administration and exercise were combined , blood glucose concentrations declined more markedly . Serum insulin concentrations showed a physiological decrease during exercise and placebo administration . If patients rested after administration of glibenclamide  serum insulin levels rose and remained elevated . When exercise and glibenclamide were combined the rise in serum insulin levels was blunted and insulin levels fell once exercise was begun . Thus , exercise attenuates the glibenclamide induced increase in serum insulin in moderately hyperglycaemic Type 2 diabetic patients . Nevertheless , exercise has a substantial hypoglycaemic effect in glibenclamide treated Type 2 diabetic patients Objective : Severe sulfonylurea-induced hypoglycemia ( SH ) remains a life-threatening and under-reported condition . We investigated the incidence of SH and clinical characteristics of patients with type 2 diabetes mellitus ( T2DM ) to demonstrate typical risk constellations . Methods : In a prospect i ve population -based observational study , all consecutive cases of SH in the period 2000 – 2009 in a German area with 200,000 inhabitants were registered .  Severe hypoglycemia was defined as a symptomatic event requiring treatment with intravenous glucose and was confirmed by a blood glucose measurement of < 50 mg/dl . Results : A mean incidence of seven episodes of SH per year and 100,000 inhabitants was registered . The 139 hypoglycemic individuals had been treated with glimepiride ( n = 98 ) , glibenclamide ( n = 40 ) or gliquidone ( n = 1 ) . No preparation showed a constant dose – effect relationship , SH occurring within a wide dose range . The patients were characterized as follows : age 77.5 ± 9.4 years , duration of diabetes 11 ± 7 years , body mass index 26.3 ± 4.9 kg/m2 , HbA1c 6.6 ± 1.3 % , creatinine clearance 46 ± 24 ml/min with renal insufficiency in 73 % and co-medication 7 ± 3 drugs . Two-thirds of all subjects lived independently at home whereas a third were cared for by a home nursing service or received care in nursing homes . In all , 30 % had participated in diabetes education programs . In 31 % , systematic blood glucose monitoring was performed . Conclusions : Uncritical prescription of sulfonylureas neglecting crucial contraindications – particularly renal insufficiency – and deficiencies of diabetes care contributed substantially to the risk of SH in the mainly geriatric patients . There is a need for alternative therapeutic concepts that minimize the risk of hypoglycemia in geriatric patients with T2DM OBJECTIVE To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System ( CGMS ) . DESIGN Open r and omized crossover comparing 3(1/2 ) months of multiple daily injections ( MDI ) and continuous subcutaneous insulin infusion ( CSII ) . SETTING Tertiary care , university-affiliated medical center . Patients Twenty-three children and adolescents with type 1 diabetes mellitus . INTERVENTIONS The CGMS was applied for 72 hours after 1 month and at the end of each study arm . MAIN OUTCOME MEASURES Hemoglobin A(1c ) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm . RESULTS The arms were similar for mean ( SD ) hemoglobin A(1c ) levels ( CSII , 8.0 % [ 0.8 % ] ; and MDI , 8.2 % [ 0.8 % ] ) and glucose levels . Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia ( P = .01 and .04 , respectively ) and for postpr and ial hypoglycemia and hyperglycemia ( P = .03 and .05 , respectively ) . The rate of hyperglycemia increased during CSII ( P = .03 ) , but 24-hour duration and area under the curve for hyperglycemia were similar . Compared with the first CGMS reading in each arm , the second had a longer mean duration of postpr and ial within-target glucose levels ( P = .04 ) , tendency for lower rate of diurnal hypoglycemic events ( P = .1 ) , shorter duration of nocturnal hypoglycemia ( P = .05 ) , and smaller 24-hour area under the curve for hypoglycemia ( P = .04 ) . CONCLUSIONS Intensive treatment with CSII seemed to be associated with slightly better prebreakfast , postpr and ial , and within-target glucose profiles than MDI , as well as a smaller area under the curve for hypoglycemia . Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia The lack in control of insulin release combined with an inadequate carbohydrate ( CHO ) ingestion accounts for the occurrence of frequent metabolic unbalances during exercise in type 1 diabetic patients . The aim of the study was to quantify , in these patients , the CHO requirement to prevent hypoglycemia during moderate exercise performed at different time intervals after morning subcutaneous insulin injection . Twelve type 1 diabetic patients and 12 well-matched healthy subjects  cycled 4 times for 1 hour at a constant workload . The rate of glucose oxidation was calculated continuously by indirect calorimetry throughout the exercise , while blood parameters were assessed periodically and orally given CHO were checked . CHO needed by the patients to prevent hypoglycemia decreased as the time elapsed from insulin administration increased , amounting to 0.63 + /- 0.30 , 0.44 + /- 0.32 , 0.28 + /- 0.24 , and 0.14 + /- 0.18 g/kg after 1 , 2.5 , 4 , and 5.5 hours , respectively . Total glucose requirement during moderate exercise ( sum of alimentary and extracellular source ) was correlated ( r = 0.739 , P < .001 ) to plasma insulin concentration , but not with fitness level . Time elapsed from last insulin dose is not a factor influencing the risk of hypoglycemia during exercise when a proportional , appropriate amount of CHO is ingested BACKGROUND Continuous glucose monitoring ( CGM ) has been shown to improve glycemic control and reduce hypoglycemia with consistent use . Youth , however , are unlikely to use CGM consistently . We compared psychological characteristics of youth with type 1 diabetes , their parents , and adults with type 1 diabetes r and omized to CGM or st and ard blood glucose monitoring ( BGM ) .  This study was an ancillary study , and participants completed the question naires at the 6-month visit of the main study . SUBJECTS AND METHODS Participants enrolled at a single site of the Juvenile Diabetes Research Foundation CGM trial completed question naires and provided diabetes management data . Participants were r and omized to the CGM or BGM group for 6 months . RESULTS Parents in both groups reported more fear of hypoglycemia than youth in the corresponding groups . CGM youth and parents reported more negative affect around BGM than those in the BGM group . CGM youth reported more trait anxiety than BGM youth , whereas CGM adults reported less state and trait anxiety than BGM adults .  CGM parent-proxy report of depression was significantly higher than that reported by BGM parents . CONCLUSIONS Youth , their parents , and adults report different psychological impacts of CGM use . In some groups and with some variables , CGM use was associated with a positive psychosocial impact , whereas in others CGM use was associated with a negative psychosocial impact . Future research should explore the psychological consequences of CGM use OBJECTIVE Continuous glucose monitoring ( CGM ) has been demonstrated to improve glycemic control in adults with type 1 diabetes but less so in children . We design ed a study to assess CGM benefit in young children aged 4 to 9 years with type 1 diabetes . RESEARCH DESIGN AND METHODS After a run-in phase , 146 children with type 1 diabetes ( mean age 7.5 ± 1.7 years , 64 % on pumps , median diabetes duration 3.5 years ) were r and omly assigned to CGM or to usual care . The primary outcome was reduction in HbA1c at 26 weeks by ≥0.5 % without the occurrence of severe hypoglycemia . RESULTS The primary outcome was achieved by 19 % in the CGM group and 28 % in the control group ( P = 0.17 ) . Mean change in HbA1c was −0.1 % in each group ( P = 0.79 ) . Severe hypoglycemia rates were similarly low in both groups . CGM wear decreased over time , with only 41 % averaging at least 6 days/week at 26 weeks . There was no correlation between CGM use and change in HbA1c ( rs = −0.09 , P = 0.44 ) . CGM  wear was well tolerated , and parental satisfaction with CGM was high . However , parental fear of hypoglycemia was not reduced . CONCLUSIONS CGM in 4- to 9-year-olds did not improve glycemic control despite a high degree of parental satisfaction with CGM . We postulate that this finding may be related in part to limited use of the CGM glucose data in day-to-day management and to an unremitting fear of hypoglycemia . Overcoming the barriers that prevent integration of these critical glucose data into day-to-day management remains a challenge [ Purpose ] This study evaluated the effects of 12 weeks combined aerobic and resistance exercise on heart rate variability in patients with Type 2 diabetes mellitus . [ Subjects and Methods ] The subjects were 16 female patients with Type 2 diabetes mellitus selected among the participants of a chronic disease management exercise class at C Region Public Health Center in South Korea . Subjects were r and omly assigned to the exercise group ( n=8 ; age , 55.97 ± 7.37 ) or the control group ( n=8 ; age , 57.53 ± 4.63 ) The exercise group performed aerobic and resistance exercises for 60 minutes per day , 3 times per week for 12 weeks . Anthropometric measurements , biochemical markers , physical fitness , and heart rate variability were examined . [ Results ] After 12 weeks of  exercise , weight , body fat percentage , waist circumference , blood glucose , insulin resistance , glycated hemoglobin level , systolic blood pressure , and diastolic blood pressure significantly decreased and cardiorespiratory fitness and muscular strength significantly increased in the exercise group . Although heart rate variability measures showed favorable changes with the exercise program , none were significant . [ Conclusion ] Although the exercise program did not show notable changes in heart rate variability in patients with Type 2 diabetes within the timeframe of the study , exercise may contribute to the prevention and control of cardiovascular autonomic neuropathy OBJECTIVE To analyze the effects of a home-based physical exercise program on quality of life , metabolic control , and anthropometric and biochemical parameters in people over 60 years of age with type 2 diabetes mellitus . METHODS Eighty-four Spanish patients aged over 60 years were finally r and omized to participate in a home-based , combined physical exercise program ( aerobic and anaerobic exercises ) or to receive conventional treatment for diabetes . At 6 months , effects on quality of life ( EuroQoL question naire ) . HbA1c , fasting glucose , hypoglycemic events , weight , BMI , waist circumference , blood pressure , and biochemical parameters were assessed . RESULTS Mean age of study participants was 66.7 ( 8.0 ) years . Patients in the exercise group showed an improved quality of life at six months based on EuroQol : 0.48 ( 0.38 ) vs 0.66 ( 0.35 ) and analogic scale 67.97 ( 18.92 ) vs 76.26 ( 20.14 ) . An improved glycemic control was also seen : HbA1c 6.35 vs 6.0 % and fasting glucose 151.2 ( 36.7 ) vs 137.6 ( 23.5 ) mg/dL , as well as a weight reduction by 1.7 kg . Hypoglycemic events did not increase . No benefits were seen in the control group . Ten subjects withdrew from the study before 6 months . CONCLUSIONS A home-based physical exercise program improves quality of life , glycemic control , and weight in type 2 diabetic patients older than 60 years Context Clinicians often split evening insulin dosing ( short-acting insulin at dinner and long-acting insulin at bedtime rather than both types with dinner ) to avoid nocturnal hypoglycemia in patients with type 1 diabetes mellitus . Although split dosing makes sense theoretically , no rigorous studies have examined its effects on glycemic control . Contribution In this r and omized , controlled crossover trial , episodes of nocturnal hypoglycemia were less frequent and fasting blood glucose and hemoglobin A1c levels were lower with split evening insulin than with mixed dosing at dinner . Clinical Implication s This study supports splitting evening insulin dosing to improve glycemic control in patients with intensively treated type 1 diabetes . The Editors Nocturnal hypoglycemia is common in patients with type 1 diabetes mellitus ( 1 - 7 ) . When insulin treatment is intensified to achieve near-normoglycemia , the frequency of hypoglycemia increases ; approximately half of these episodes occur at night ( 2 , 3 ) . Unrecognized nocturnal hypoglycemia is common ( 1 , 3 - 8 ) . Overtreatment of symptomatic nocturnal hypoglycemia with snacks often results in hyperglycemia the next day ( 9 - 11 ) . Asymptomatic nocturnal hypoglycemia can cause morning headache and malaise and may result in diminished awareness , reduced responses of adrenaline , and adaptation of cognitive function during the episode ( 12 - 15 ) . Recurrent nocturnal hypoglycemia may contribute to the vicious cycle of hypoglycemia unawareness and impaired hormonal counterregulation in patients with type 1 diabetes , leading to increased risk for severe hypoglycemia ( 16 ) . The nonphysiologic pharmacokinetics and pharmacodynamics of insoluble , intermediate-acting insulin preparations , such as neutral protamine Hagedorn ( NPH ) insulin , play a central role in inducing nocturnal hypoglycemia in type 1 diabetes ( 4 ) . When injected at dinner , NPH insulin results in excess plasma insulin bioavailability at approximately midnight , a time at which patients with type 1 diabetes are more insulin sensitive ( 17 , 18 ) ; thus , the risk for hypoglycemia increases between midnight and 3:00 a.m. Later , insulin deficiency develops at dawn ( 4 , 18 ) and contributes to fasting hyperglycemia . When the nocturnal peak plasma level of insulin produced by an evening injection of intermediate-acting ( NPH ) insulin is postponed by 3 to 4 hours as a result of injecting NPH insulin at bedtime instead of at dinner , fasting and postbreakfast blood glucose levels decrease ( 19 ) . Although the pharmacokinetics and pharmacodynamics of NPH insulin would suggest that splitting of the evening insulin regimen ( administering short-acting insulin at dinner and NPH insulin at bedtime ) should decrease the risk for nocturnal hypoglycemia , to the best of our knowledge no data indicate this in patients with type 1 diabetes mellitus . W e tested the hypothesis that in intensive treatment of type 1 diabetes , splitting the evening insulin administration rather than mixing short-acting and NPH insulin at dinner reduces the risk for nocturnal hypoglycemia and improves glycemic control , awareness of hypoglycemia , and counterregulation to hypoglycemia . Although split dosing makes sense theoretically , no rigorous studies have examined its effects on glycemic control . Methods Patients We recruited 22 patients ( 10 women , 12 men ; mean age [ SD ] , 29 3 years ) with type 1 diabetes mellitus ( mean duration of diagnosed diabetes [ SD ] , 14 2 years ) receiving long-term intensive insulin treatment ( multiple insulin injections with regular human insulin before meals and NPH insulin at bedtime ) from the outpatient Diabetes Clinic of the Department of Internal Medicine at the University of Perugia . At baseline , the mean ( SD ) body mass index of the cohort was 23 1 kg/m2 , and the mean ( SD ) hemoglobin A1c value was 6.7 % 0.4 % . Patients had no detectable microangiopathic complications ; autonomic neuropathy , as assessed by using a st and ard battery of cardiovascular tests [ 20 ]  ; peripheral neuropathy ; or microalbuminuria . The patients had no history or clinical evidence of hypertension and were taking no medications other than insulin . We excluded 1 ) patients with hypoglycemia unawareness , defined as an absence of symptoms while the blood glucose level is approximately 2.5 to 2.8 mmol/L [ 45 to 50 mg/dL ] and 2 ) patients with a history of severe hypoglycemia , defined as episodes of hypoglycemia requiring assistance from another person in the previous year . All patients in the study gave informed consent . The Institutional Review Board of University of Perugia in Perugia , Italy , approved this study . Study Design After a 1-month run-in period , during which patients continued their usual regimen of multiple daily insulin injections , we r and omly assigned patients to receive one of the two following treatment regimens for the first 4-month treatment period : 1 ) a continued regimen of four daily insulin injections ( evening split treatment)that is , administration of regular insulin before dinner and NPH insulin at bedtime [ usually between 10:30 p.m. and 11:00 p.m. ] or 2 ) a regimen of regular insulin at breakfast and lunch and a mixture of regular and NPH insulins at dinner ( evening mixed treatment ) . Thereafter , the patients were switched to the other treatment for an additional 4 months . Insulin ( short-acting and NPH ) was administered with syringes to achieve the target values for fasting blood glucose of 5.0 to 6.7 mmol/L ( 90 to 120 mg/dL ) before meals and at bedtime [ 2 ] . The dose of mealtime regular insulin was titrated on the basis of the blood glucose measurement obtained 1 ) before the meal and 2 ) on the previous day , 4 to 5 hours after that meal , or , in the case of the evening meal , at bedtime . The dose of NPH insulin given at dinner or at bedtime was titrated on the basis of the predinner or bedtime blood glucose level , respectively . The patients were instructed to measure capillary blood glucose levels by using Reflolux S ( Boehringer Mannheim , Mannheim , Germany ) before each insulin injection , at bedtime , and every other day at 3:00 a.m. The patients were also asked to skip no more than one of their daily capillary glucose measurements and to keep diaries of blood glucose values , insulin dosage , and hypoglycemic episodes ( blood glucose level 4.0 mmol/L [ 72 mg/dL ] ) occurring any time during the day . To prevent nocturnal hypoglycemia , the patient instructions included a suggestion to consume a snack containing approximately 20 g of carbohydrates ( approximately 20 g of bread and approximately 60 mL of 2 % milk ) when the capillary blood glucose level at bedtime was less than 7.0 mmol/L ( < 126 mg/dL ) with the evening mixed treatment and less than 6.0 mmol/L ( < 108 mg/dL ) with the evening split treatment . We also suggested that patients have a similar snack if the blood glucose level at 3:00 a.m. was 4.0 mmol/L or less ( 72 mg/dL ) at any time during the night . If such a snack did not relieve hypoglycemic symptoms in approximately 10 minutes , patients were told to have another snack ( for a total of 40 g of carbohydrates ) . Throughout the study , patients visited the outpatient clinic monthly to su bmi t their diaries and had frequent telephone contacts ( every 3 to 6 days ) with the investigators . At the end of each treatment period , patients were admitted to the clinical research unit of the hospital , where blood glucose was monitored overnight ; the next morning , counterregulatory and symptomatic responses to hypoglycemia and cognitive performance were evaluated during a hyperinsulinemic , stepped hypoglycemic clamp study . Hemoglobin A1c values were measured before r and omization and at the end of both treatment periods . In-Hospital Evaluation Overnight Testing Patients were admitted for overnight evaluations after dinner ( and , thus , after premeal insulin administration ) , at approximately 9:00 p.m. A h and vein of the nondominant arm was cannulated retro grade ly , and the h and was maintained in a hot pad ( approximately 60 C ) for sampling of arterialized-venous blood ( 21 ) . A second venous line of the ipsilateral arm was cannulated for intravenous infusion of glucose whenever an infusion was needed to prevent hypoglycemia ( that is , to prevent a decrease in plasma glucose level to 4.0 mmol/L [ 72 mg/dL ] ) . Glucose was infused whenever the plasma glucose level decreased to less than 4.4 mmol/L ( < 80 mg/dL ) . On overnight stays , patients were allowed to watch television until 11:00 p.m. , at which time patients receiving the evening split regimen had their bedtime injection of NPH insulin . Overnight , patients gave blood sample s for measurement of plasma glucose and insulin levels every 30 minutes . Stepped Hypoglycemic Clamp Studies At 8:30 a.m. on the following morning , a variable intravenous infusion of human regular insulin ( diluted to 1 U/mL in 2 mL of the patient 's blood and sodium chloride [ NaCl 0.9 % ] to a final volume of 100 mL ) was begun to maintain a plasma glucose level of 5.0 mmol/L ( 90 mg/dL ) . Infusion continued until 10:00 a.m. For this procedure , which was done according to a previously described algorithm ( 22 ) , we used an intravenous syringe pump ( Harvard Apparatus , Ealing , South Natick , Massachusetts ) . At 10:00 a.m. , the rate of  intravenous insulin infusion  was increased to 1 mU/kg 1 min 1 until 2:30 p.m. ( 270 minutes ) , followed by 2 mU/kg 1 min 1 for an additional 90 minutes , until 4:00 p.m. ( time , 360 minutes ) . Plasma glucose was clamped by variable glucose infusion at sequential target glucose values of 4.3 , 3.7 , 3.0 , and 2.3 mmol/L ( 78 , 66 , 54 , and 42 mg/dL ) ; at each target level , blood was drawn to measure hormone and metabolite levels , and patients were assessed for symptoms of hypoglycemia and for cognitive function ( 23 - 25 ) . Symptoms were quantified by asking the patients to score ( on a scale in which 0 = none and 5 = severe ) each of the following symptoms : dizziness , tingling , blurred vision , difficulty in thinking , faintness , anxiety , palpitations , hunger , sweating , irritability , The prevalence of obesity and diabetes continues to rise in the US . Glucagon-like peptide-1 receptor agonist ( GLP-1RA ) is an effective treatment option for type 2 diabetes mellitus ( T2DM ) that promotes weight loss . Common and effective treatment options added to metformin therapy ( basal insulin , sulfonylureas , and pioglitazone ) contribute to weight gain , which makes the addition of GLP-1RAs advantageous . Exenatide was the first agent in this class and has recently been approved for use in combination with insulin glargine by the US Food and Drug Administration and the European Medicines Agency . Until recently , there was a lack of data examining basal insulin combined with these agents . The main purpose of this article is to review the prospect i ve interventional data on the safety and efficacy of GLP-1RAs ( exenatide , liraglutide , albiglutide , lixisenatide ) combined with basal insulin therapy in nonpregnant adults with T2DM . Data bases search ed were PubMed , Cochrane Central Register of Controlled Trials and the Data base of Systematic Review s ( inception to January 2012 ) . Abstract s presented at relevant diabetes and endocrine meetings from 2009 to 2011 were also review ed , as were reference lists of identified publications . A total of five studies met the criteria and were included in the review . Data from these studies demonstrated that this combination therapy offers advantages for the treatment of diabetes , such as additional lowering of A1c without major risk for hypoglycemia , lower basal insulin requirements , decreased postpr and ial glucose levels ( with or without fasting plasma glucose decreases ) , and weight loss , or at the very least , less weight gain . However , the gastrointestinal side effects and high cost of these agents may limit their use . This review demonstrates that adding a GLP-1RA to an existing basal insulin regimen is a reasonable treatment strategy in nonpregnant adult patients with T2DM Objective To explore the experiences of adolescents with type 1 diabetes mellitus ( T1DM ) and their parents taking part in an overnight closed loop study at home , using qualitative and quantitative research methods . Research design and methods Adolescents aged 12–18 years on insulin pump therapy  were recruited to a pilot closed loop study in the home setting . Following training on the use of a study insulin pump and continuous glucose monitoring ( CGM ) , participants were r and omized to receive either real-time CGM combined with overnight closed loop or real-time CGM alone followed by the alternative treatment for an additional 21 days with a 2–3-week washout period in between study arms . Semistructured interviews were performed to explore participants ’ perceptions of the impact of the closed loop technology . At study entry and again at the end of each 21-day crossover arm of the trial , participants completed the  Diabetes Technology Question naire ( DTQ ) and Hypoglycemia Fear Survey ( HFS ; also completed by parents ) . Results 15 adolescents and 13 parents were interviewed . Key positive themes included reassurance/peace of mind , confidence , ‘ time off ’ from diabetes dem and s , safety , and improved diabetes control . Key negative themes included difficulties with calibration , alarms , and size of the devices . DTQ results reflected these findings . HFS scores were mixed . Conclusions Closed loop insulin delivery represents cutting-edge technology in the treatment of T1DM . Results indicate that the psychological and physical benefits of the closed loop system outweighed the practical challenges reported . Further research from longitudinal studies is required to determine the long-term psychosocial benefit of the closed loop technology OBJECTIVE Appropriate glycemic control is fundamental to diabetes care , but aggressive glucose targets and intensive therapy may unintentionally increase episodes of hypoglycemia . We quantified the burden of severe hypoglycemia requiring medical intervention in a well-defined population of insured individuals with diabetes receiving care in integrated health care delivery systems across the U.S. RESEARCH DESIGN AND METHODS This observational cohort study included 917,440 adults with diabetes receiving care during 2005 to 2011 at participating SUrveillance , PREvention , and ManagEment of Diabetes Mellitus ( SUPREME-DM ) network sites .  Severe hypoglycemia rates were based on any occurrence of hypoglycemia-related ICD-9 codes from emergency department or inpatient medical encounters and reported overall and by age , sex , comorbidity status , antecedent A1C level , and medication use . RESULTS Annual rates of severe hypoglycemia ranged from 1.4 to 1.6 events per 100 person-years . Rates of severe hypoglycemia were higher among those with older age , chronic kidney disease , congestive heart failure , cardiovascular disease , depression , and higher A1C levels , and in users of insulin , insulin secretagogues , or β-blockers ( P < 0.001 for all ) . Changes in severe hypoglycemia occurrence over time were not clinical ly significant in the cohort as a whole but were observed in subgroups of individuals with chronic kidney disease , congestive heart failure , and cardiovascular disease . CONCLUSIONS Risk of severe hypoglycemia in clinical setting s is considerably higher in identifiable patient subgroups than in r and omized controlled trials . Strategies that reduce the risk of hypoglycemia in high-risk patients are needed Physical inactivity is highly common in adults with type 1 diabetes ( T1D ) as specific barriers ( i.e. , hypoglycemia ) may prevent them from being active . The objective of this study was to examine the efficacy of the Physical Exercise Promotion program in type 1 diabetes ( PEP-1 ) program , a group program of physical activity ( PA ) promotion ( intervention ) compared with an information leaflet ( control ) , to improve total energy expenditure ( TEE ) in adults with T1D after 12 weeks . TEE was measured with a motion sensor over a 7-day period at inclusion , after the program ( 12 weeks ) and 1-year after inclusion . The 12 weekly sessions of the program included a 30-min information session ( glycemic control and PA ) and 60 min of PA .  A total of 48 adults , aged 18 to 65 years with a reported PA practice < 150 min per week , were recruited ( 45.8 % men ; aged 44.6 ± 13.3 years ; 8.0 % ± 1.1 % glycated hemoglobin ( A1c ) ) and r and omized in this pilot trial . Ninety percent of participants completed the program and 88 % completed the 1-year follow-up . No change was observed for TEE and A1c in both groups . After the 12-week program , the mean peak oxygen uptake increased ( 14 % ; p = 0.003 ) in the intervention group ; however , at the 1-year follow-up , it was no longer different from baseline . In the control group , no difference was observed for the peak oxygen uptake . These results suggest that the PEP-1 pilot program could increase cardiorespiratory fitness . However , this benefit is not sustained over a long-term period . The PEP-1 program did not increase TEE in patients with T1D and other strategies remain necessary to counteract physical inactivity in this population Severe hypoglycemia ( SH ) can be a significant problem for patients around the world with Type 1 Diabetes Mellitus ( T1DM ) . To avoid SH , patients need to better manage , and reduce the occurrence of , preceding mild hypoglycemia . Hypoglycemia Anticipation , Awareness and Treatment Training ( HAATT ) , developed in the United States specifically to address such issues , was evaluated at short- and long-term follow-up in a medically , economically and culturally different setting ; Bulgaria . Sixty adults with T1DM and a history of recurrent SH ( 20 each from Sofia , Russe , and Varna , Bulgaria ) were r and omized to Self-Monitoring of Blood Glucose ( SMBG ) or SMBG+ HAATT . For 6 months before and 1 to 6 and 13 to 18 months after intervention , participants recorded occurrence of moderate , severe , and nocturnal hypoglycemia . For 1-month pre- and post-intervention , participants completed daily diaries concerning their diabetes management . Relative to SMBG , HAATT produced significant improvement in occurrence of low BG , moderate , severe , and nocturnal hypoglycemia , and detection and treatment of low BG ( p values < .05 to < .001 ) , with no compromise in metabolic control . At long-term follow-up , HAATT participants continued to have significantly fewer episodes of moderate and severe hypoglycemia . These findings suggest that a structured , specialized psycho-educational treatment program ( HAATT ) can be highly effective in managing hypoglycemia Summary Objective : To compare the plasma glucose ( PG ) response with a fixed mixture of 25 % insulin lispro and 75 % NPL ( Mix25 ) , prior to a meal and 3 h before exercise , to human insulin 30/70 ( 30/70 ) in patients with type 2 diabetes . Research design and methods : Thirty-seven patients were treated in a r and omized , open-label , 8-week , two-period crossover study . Mix25 was injected 5 min before breakfast and dinner throughout the study , as was 30/70 on inpatient test days and on outpatient dose titration days . Following the 4-week outpatient phase , patients were hospitalized , and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min , separated by 30 min rest , starting 3 h after a 339 kcal breakfast .  Results : The 2-h postpr and ial PG was significantly lower with Mix25 ( ( mean ± SEM ) 10.5 ± 0.4 mmol/lvs 11.6 ± 0.4 mmol/l ; p = 0.016 ) . Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 ( -3.6 ± 0.29 mmol/l vs -4.7 ± 0.31 mmol/l ; p = 0.001 ) . The maximum decrease in PG over 6 h , after exercise onset , was significantly less with Mix25 ( -4.3 ± 0.4 mmol/l vs -5.9 ± 0.4 mmol/l ; p < 0.001 ) . The frequency of hypoglycemia ( blood glucose ( BG ) < 3 mmol/l or symptoms ) during the inpatient test was not different between treatments . During the outpatient phase , the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 ( 0.7 ± 0.2 episodes/30d vs 1.2 ± 0.3 episodes/30 d ; p = 0.042 ) . Conclusions : Mix25 result ed in better postpr and ial PG control without an increase in exercise-induced hypoglycemia . The smaller decrease in PG during the postpr and ial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70 , especially for patients in tight glycemic control PURPOSE Hospitalized patients with type 2 diabetes mellitus traditionally receive insulin on a sliding-scale regimen , but the benefits of this approach are unclear . The purpose of this study was to compare the effects of the sliding scale insulin regimen with those of routine diabetes medications on hyperglycemia , hypoglycemia and length of hospitalization in diabetic patients hospitalized for other conditions . METHODS This was a multicenter , r and omized controlled trial conducted in family medicine inpatient services . One hundred fifty-three patients with type 2 diabetes mellitus hospitalized for other conditions were r and omized to receive routine diabetes medications ( control ) or the combination of a st and ard sliding-scale insulin regimen and routine diabetes medications ( intervention ) . The outcome measures included frequency of hyperglycemia and hypoglycemia ( glycemic events ) , and length of hospitalization . RESULTS No differences were identified between treatment groups in the frequency of glycemic events . In the intervention group , 33.3 % of patients developed hyperglycemia compared to 34.6 % in the control group ( P = .87 ) . Six patients developed hypoglycemia in the intervention group , compared with 7 in the control group ( P = .83 ) . There was no difference in length of hospitalization ( P = .86 ) . Regardless of treatment assignment , patients receiving intermediate-acting insulin ( OR , 2.8 ; 95 % CI , 1.2–6.5 ) , those with blood glucose values greater than 250 mg/dL at baseline ( OR , 6.3 ; 95 % CI , 2.3 – 17.2 ) and those receiving corticosteroids ( OR , 9.1 ; 95 % CI , 3.1 – 27.0 ) were more likely to have glycemic events . CONCLUSIONS The use of the sliding scale insulin regimen in combination with routine diabetes medications does not affect the rate of hyperglycemia , hypoglycemia or length of hospitalization in patients with type 2 diabetes mellitus hospitalized for other conditions
For blood glucose there was little difference between groups at any time point .
Objective Type 1 diabetes mellitus rates are rising worldwide .
The health benefits of physical exercise in this condition are many , but more than 60 % do not participate , mainly from fear of hypoglycemia .
This systematic review explores the effects of physical exercise modes on blood glucose levels in adults for hypoglycemia prevention .