Hypoglycaemia in insulin-treated Type 2 diabetes: frequency,symptoms and impaired awareness

Aims Hypoglycaemia is considered to be less common in people with insulin-treated Type 2 diabetes than in Type 1 diabetes. A retrospective survey was made of 215 people with insulin-treated Type 2 diabetes to quantify the frequency and nature of hypoglycaemia experienced. Methods The frequencies of mild (self-treated) and severe (required assistance) hypoglycaemia during the preceding year were estimated retrospectively. The usual symptoms of hypoglycaemia and state of awareness of hypoglycaemia were scored using validated questionnaires and any history suggestive of impaired hypoglycaemia awareness was documented. Results In this cohort, 157 (73%) had experienced hypoglycaemia since commencing insulin, the frequency of which increased with duration of diabetes and of insulin therapy and was inversely related to current HbA_1c (all P < 0.05). During the preceding year, 32 individuals (15%) had experienced severe hypoglycaemia, with an estimated incidence for the entire group of 0.28 episodes/patient/year. Principal components analysis revealed two underlying symptom groups (autonomic and neuroglycopenic), similar to those reported previously by young adults with Type 1 diabetes, but the total symptom score declined with advancing age. Of the 157 with a history of hypoglycaemia, the 13 (8%) individuals who gave a history of impaired awareness of hypoglycaemia had experienced a ninefold higher incidence of severe hypoglycaemia than those with normal awareness, and reported experiencing mainly neuroglycopenic symptoms. Conclusions While the overall frequencies of mild and severe hypoglycaemia were lower in insulin-treated Type 2 diabetes than have been reported previously in Type 1 diabetes, the risk of hypoglycaemia was greater with increasing duration of diabetes and of insulin therapy. Although impaired awareness of hypoglycaemia was uncommon, it was associated with a higher incidence of severe hypoglycaemia. Diabet. Med. 20, ***–*** (2003)     

Are bedtime nutritional strategies effective in preventing nocturnal hypoglycaemia in patients with type 1 diabetes?

Hypoglycaemia remains the major limiting factor for adequate diabetes control for patients with type 1 diabetes (T1D), especially during the night‐time. Although nutritional strategies for nocturnal hypoglycaemia (NH) prevention are regularly suggested in clinical practice, there is no evidence‐based recommendation for the usefulness and optimal composition of a bedtime snack. The aim of this narrative review was to analyse the current state of knowledge on nutritional strategies to prevent NH in individuals with T1D. A literature search was conducted, using PubMed and Medline (1946 to 2013); 16 studies were retrieved. Overall, the level of evidence was low. Results indicated that a calibrated bedtime snack based on bedtime blood glucose (BG) level could be effective to reduce NH occurrence for patients treated with human or animal insulin (short‐acting combined with lente, ultralente and/or intermediate‐acting insulin), but there is no evidence for patients treated with insulin analogues as part of multiple daily injections or insulin pump regimen. Some evidence suggests that including uncooked cornstarch or alanine in the bedtime snack composition could provide some benefits for the prevention of NH. Individualized recommendations of a bedtime snack intake for patients or situations at high risk for NH (long standing diabetes, hypoglycaemia unawareness, prior physical activity, alcohol consumption, bedtime BG close to hypoglycaemia threshold) appear as a prudent recommendation. On the basis of the available evidence, a bedtime snack cannot be recommended systematically but it might be useful if prescribed in an individualized fashion; further research is needed to evaluate these strategies.     

Hypoglycaemia in Type 2 diabetes

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self‐reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications.     

A randomized pilot study in Type 1 diabetes complicated by severe hypoglycaemia, comparing rigorous hypoglycaemia avoidance with insulin analogue therapy, CSII or education alone.

AIM: To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-standing Type 1 diabetes (T1DM). METHODS: Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were randomized in a pilot 24-week prospective study to optimized analogue therapy (ANALOGUE; lispro/glargine); continuous subcutaneous insulin infusion therapy (CSII; lispro); or re-education with relaxation of blood glucose targets on existing conventional insulin regimen (EDUCATION). Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose. RESULTS: Further severe hypoglycaemia was prevented in five participants (71%) in each group (P = 0.06). Incidence of severe hypoglycaemia was: 0.6 (ANALOGUE), 0.9 (CSII), and 3.7 (EDUCATION) episodes per patient year. Restoration of hypoglycaemia awareness was confirmed by validated questionnaire in three (43%) ANALOGUE, four (57%) CSII and five (71%) EDUCATION patients. Glycated haemoglobin (HbA1c) was significantly improved in the ANALOGUE group between weeks 0 and 24 (8.6 +/- 1.1 vs. 7.6 +/- 0.8%; P = 0.04 for change). Non-significant improvement was seen in the CSII group (8.5 +/- 1.9 vs. 7.4 +/- 1.0%; P = 0.06). No change in HbA1c was seen in the EDUCATION group (8.5 +/- 1.1 vs. 8.3 +/- 1.0%; P = 0.54). There were no episodes of diabetic ketoacidosis or any other adverse events in any group. CONCLUSIONS: In this pilot randomized trial comparing optimized ANALOGUE, CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia, we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups.     

Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes: a cross-sectional survey.

AIMS: The reported risk of severe hypoglycaemia in insulin-treated Type 2 diabetes is highly variable and few studies have evaluated the influence of risk factors. We assessed the incidence and the influence of potential risk factors for severe hypoglycaemia in a questionnaire survey in subjects with insulin-treated Type 2 diabetes receiving currently recommended multifactorial intervention. METHODS: Consecutive patients with insulin-treated Type 2 diabetes (n = 401) completed a questionnaire about occurrence of hypoglycaemia in the past, hypoglycaemia awareness and socio-demographic factors. A zero-inflated negative binomial model was used to assess the influence of potential risk factors on the rate of severe hypoglycaemia. RESULTS: The overall incidence of severe hypoglycaemia in the preceding year was 0.44 episodes/person year. Sixty-six (16.5%) patients had experienced at least one event. The risk of any episode of severe hypoglycaemia positively correlated with impaired hypoglycaemia awareness, being married and long duration of diabetes. The risk of repeated episodes of severe hypoglycaemia positively correlated with the presence of peripheral neuropathy, while long duration of diabetes prior to insulin treatment and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists (ARBs) were associated with reduced risk. C-peptide concentration and HbA1c were not associated with the risk of severe hypoglycaemia. CONCLUSIONS: In this cohort of insulin-treated Type 2 diabetic patients, the incidence of severe hypoglycaemia is higher than reported in most studies, corresponding to about one-third of that in Type 1 diabetes. Impaired hypoglycaemia awareness is the most important risk factor for severe hypoglycaemia.     

Frequency,Severity and Symptomatology of Hypoglycaemia: a Comparative Trial of Human and Porcine Insulins in Type 1 Diabetic Patients

A randomized, double-blind, cross-over trial was performed to compare the frequency, severity, and symptomatology of hypoglycaemia during treatment with porcine and human insulins. Forty patients with Type 1 diabetes (20 newly diagnosed and 20 with diabetes of 5–20 years duration) were treated with human and porcine insulins for consecutive 3-month periods, in random order. Episodes of hypoglycaemia were recorded prospectively with self-reporting of the presence and intensity of symptoms using a standardized scoring technique. Serial measurements of glycated haemoglobin and review of home blood glucose tests confirmed that similar glycaemic control was achieved with each insulin species. On comparison of the treatment periods with human and porcine insulins, no differences were demonstrated in the total frequency of symptomatic hypoglycaemia (3.10 vs 3.06 episodes patient^?1 3-months^?1; p = 0.94), the frequency of severe hypoglycaemia (0.1 vs 0.2 episodes patient^?1 3-months^?1; p = 0.44), the occurrence of asymptomatic biochemical hypoglycaemia (0.75 vs 0.68 episodes patient^?1 3-months^?1; p = 0.81), and the capillary blood glucose concentration at the onset of hypoglycaemic symptoms (2.6 ± 0.2 vs 2.4 ± 0.3 mmol I^?1; p = 0.40), with all results being expressed for human vs porcine treatment periods, respectively. The symptoms of hypoglycaemia did not differ during the treatment periods with each insulin species. In conclusion, treatment with human insulin had no effect upon the symptomatic response to hypoglycaemia, did not increase the total frequency of hypoglycaemia, and did not emerge as a significant risk factor for severe hypoglycaemia in these patients.     

Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study.

AIMS: To ascertain the frequency and identify predictors of self-reported hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes. METHODS: A random sample of 267 people with insulin-treated diabetes were recruited from a population-based diabetes register in Tayside, Scotland. Each subject prospectively recorded the number of mild and severe hypoglycaemic episodes experienced over a 1-month period. Ordinal logistic regression was performed to identify potential predictors of hypoglycaemia. RESULTS: Five hundred and seventy-two hypoglycaemic events were reported by 155 patients. The participants with Type 1 diabetes had a total of 336 hypoglycaemic events with a rate of 42.89 events per patient per year. Of these, nine were severe hypoglycaemic events, with a rate of 1.15 events per patient per year. Participants with insulin-treated Type 2 diabetes experienced a total of 236 hypoglycaemic events with a rate of 16.37 events per patient per year. Of these, five were severe hypoglycaemic events, which would be equivalent to 0.35 events per patient per year. Predictors of hypoglycaemia in Type 1 diabetes were a history of previous hypoglycaemia (P = 0.006) and co-prescribing of any oral drug (P = 0.048). In patients with insulin-treated Type 2 diabetes, a history of previous hypoglycaemia (P < 0.0001) and duration of insulin treatment (P = 0.014) were significant predictors. CONCLUSION: The incidence of self-reported severe hypoglycaemia in insulin-treated Type 2 diabetes is lower than in Type 1 diabetes but does occur more often than previously reported and with sufficient frequency to cause significant morbidity. Duration of insulin treatment is a key predictor of hypoglycaemia in insulin-treated Type 2 diabetes.     

Hypoglycaemia incidence and recovery during home use of hybrid closed‐loop insulin delivery in adults with type 1 diabetes

Glucose excursion was assessed prior to and post hypoglycaemia to increase understanding of hypoglycaemia incidence and recovery during hybrid closed‐loop insulin delivery. We retrospectively analysed data from 60 adults with type 1 diabetes who received, in a crossover randomized design, day‐and‐night hybrid closed‐loop insulin delivery and insulin pump therapy, the latter with or without real‐time continuous glucose monitoring. Over 4‐week study periods, we identified hypoglycaemic episodes, defined as sensor glucose <3.0 mmol/L, and analysed sensor glucose relative to the onset of hypoglycaemia. We identified 377 hypoglycaemic episodes during hybrid closed‐loop intervention vs 662 during control intervention (P < .001), with a predominant reduction of nocturnal hypoglycaemia. The slope of sensor glucose prior to hypoglycaemia was steeper during closed‐loop intervention than during control intervention (P < .01), while insulin delivery was reduced (P < .01). During both day and night, participants recovered from hypoglycaemia faster when treated by closed‐loop intervention. At 120 minutes post hypoglycaemia, sensor glucose levels were higher during closed‐loop intervention compared to the control period (P < .05). In conclusion, closed‐loop intervention reduces the risk of hypoglycaemia, particularly overnight, with swift recovery from hypoglycaemia leading to higher 2‐hour post‐hypoglycaemia glucose levels.     

Treatment and prevention of severe hypoglycaemia in people with diabetes: Current and new formulations of glucagon

Some therapies for diabetes increase the risk of hypoglycaemia, in particular all insulins and insulin secretagogues, including the glinides and sulfonylureas. Hypoglycaemia remains a major limiting factor to successful glycaemic management, despite the availability of prevention options such as insulin analogues, continuous glucose monitoring, insulin pumps, and dogs that have been trained to detect hypoglycaemia. Non-severe (self-treated) and severe (requiring assistance for recovery) hypoglycaemia rates are higher in people with type 1 diabetes, but those with insulin-treated type 2 diabetes are also at risk. Education and regular review are essential between people with diabetes and their caregivers and healthcare professionals about symptoms, prevention and treatment. Awareness of the potential dangers of hypoglycaemia is fundamental to the optimal management of diabetes. When therapy is intensified to achieve glycaemic targets, it is important that people at risk of severe hypoglycaemia, and particularly their caregivers, have ready access to effective treatment for hypoglycaemia emergencies. The current and potential formulations of glucagon available for treatment of severe hypoglycaemia are reviewed.     

Severe hypoglycaemia in children and adolescents during multiple-dose insulin therapy

Episodes of severe hypoglycaemia, resulting in coma and/or convulsions, were documented in an unselected, population-based group of 376 children and adolescents with Type 1 diabetes mellitus (Type 1 DM) treated at the Aurora Hospital, City of Helsinki. A prospective study in 1994–95 yielded 493 patient-years and a retrospective study in 1990–93, 904 patient-years of data. Of these patients, 77–85 % received insulin in three or more daily doses. During 1990–95, 43 patients had a total of 48 severe hypoglycaemic episodes. For each episode (n = 48), one control Type 1 DM patient who had never experienced any severe hypoglycaemia, matched by age, diabetes duration and puberty, was sought from the study population. Incidence of severe hypoglycaemia was 3.1/100 patient years prospectively and 3.6/100 retrospectively. At the time of the episode, median age was 13.3 (range 2.2–21) years, and median diabetes duration 6.1 (0.5–14.6) years. Rates were similar in different age groups (<6, 6–12.9 and ≥ 13 years). A potential explanation for the hypoglycaemia was found in 79 % of the episodes. Insulin dose was higher (p = 0.04) and HbA_1c lower (p = 0.005) in patients with severe hypoglycaemia than in controls. In conclusion, multiple-dose insulin therapy in young patients with Type 1 DM can be associated with a low rate of severe hypoglycaemia. The majority of such episodes seem to be preventable. © 1998 John Wiley & Sons, Ltd.     

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.     

Is insulin pump therapy effective in Type 1 diabetes?

There continues to be uncertainty about the effectiveness in Type 1 diabetes of insulin pump therapy (continuous subcutaneous insulin infusion, CSII) vs. multiple daily insulin injections (MDI). This narrative review discusses the reasons for this uncertainty, summarizes the current evidence base for CSII and suggests some future research needs. There are difficulties in interpreting trials of CSII because effectiveness varies widely due to factors such as differing baseline control, suboptimal use of best CSII practices, and psychological factors, for example, high external locus of control, non‐adherence and lack of motivation. Many summary meta‐analyses are also misleading because of poor trial selection (e.g. short duration, obsolete pumps, low baseline rate of hypoglycaemia) and reliance on mean effect size for decision‐making. Both MDI and CSII can achieve strict glycaemic control without hypoglycaemia in some people with Type 1 diabetes, especially those who are motivated and have undergone structured diabetes education, and with high levels of ongoing input from healthcare professionals. CSII is particularly effective in those people with Type 1 diabetes who have not achieved target HbA_1c levels without disabling hypoglycaemia using best attempts with MDI, and here there can be valuable and substantial improvement. Insulin pumps are safe, effective and accepted when used in newly diagnosed diabetes, particularly in children, where MDI may not be practicable. Future research needs include more studies on mortality associated with insulin pumps where registry data have suggested lower rates vs. MDI; and psychological strategies to improve non‐adherence and suboptimal glycaemic outcomes on CSII.     

Reduced nocturnal hypoglycaemia with basal insulin peglispro compared with insulin glargine: pooled analyses of five randomized controlled trials

Basal insulin peglispro (BIL) is a novel basal insulin with hepato‐preferential action, resulting from reduced peripheral effects. This report summarizes hypoglycaemia data from five BIL phase III studies with insulin glargine as the comparator, including three double‐blind trials. Prespecified pooled analyses (n = 4927) included: patients with type 2 diabetes (T2D) receiving basal insulin only, those with T2D on basal‐bolus therapy, and those with type 1 diabetes (T1D). BIL treatment resulted in a 36–45% lower nocturnal hypoglycaemia rate compared with glargine, despite greater reduction in glycated haemoglobin (HbA1c) and higher basal insulin dosing. The total hypoglycaemia rate was similar in patients with T2D on basal treatment only, trended towards being higher (10%) in patients with T2D on basal‐bolus treatment (p = .053), and was 15% higher (p < .001) with BIL versus glargine in patients with T1D, with more daytime hypoglycaemia in the T1D and T2D groups who were receiving basal‐bolus therapy. In T1D, during the maintenance treatment period (26‐52 weeks), the total hypoglycaemia rate was not significantly different. There were no differences in severe hypoglycaemia in the T1D or T2D pooled analyses. BIL versus glargine treatment resulted in greater HbA1c reduction with less nocturnal hypoglycaemia in all patient populations, higher daytime hypoglycaemia with basal‐bolus therapy in the T1D and T2D groups, and an associated increase in total hypoglycaemia in the patients with T1D.     

Long-term evaluation of a structured outpatient education programme for intensified insulin therapy in patients with Type 1 diabetes: a 12-year follow-up

Aims/hypothesis This study was conducted to evaluate the long-term outcome of a structured outpatient diabetes teaching and treatment programme (DTTP) for intensified insulin therapy in patients with Type 1 diabetes, which aims to improve metabolic control without increasing the risk of severe hypoglycaemia.Methods All 123 diabetic outpatients (age 41±14 years; 64 women; BMI 23.5±3.1; diabetes duration 17±11 years; HbA₁c 7.9±1.6%; 32 patients with a history of severe hypoglycaemia; 18 with overt nephropathy; 22 with proliferative retinopathy) who participated in the DTTP between June 1989 and June 1990 were invited for follow-up visits after 3, 6 and 12 years.Results Out of the 123 patients, 11 died during the follow-up period, two were lost for follow-up, and one was not willing to participate in re-evaluation after 12 years. Mean HbA₁c levels decreased from 7.9±1.6% to 7.1±1.2% (p<0.01) after 3 years, and were 7.8±1.5% (NS) and 7.8±1.2% (NS) after 6 and 12 years respectively. Frequency of hypoglycaemia decreased from 0.49 episodes per patient per year to 0.14 after 3 years (p<0.01), 0.19 after 6 years (p<0.01) and 0.16 after 12 years (p<0.01). Of the participants, 41% were able to lower HbA₁c levels without episodes of severe hypoglycaemia and to maintain this improvement at all follow-up visits over the 12-year period. At follow-up, intensified insulin therapy was carried out by 94% of the patients.Conclusions/interpretation A sustained reduction of the incidence of severe hypoglycaemia was observed in patients with Type 1 diabetes after participation in a structured outpatient DTTP over a 12-year period.Abbreviations DTTP diabetes teaching and treatment programme - EDIC Epidemiology of Diabetes Interventions and Complications - IIT intensified insulin therapyConflict of interest: This trial was supported in part by the Center of Excellence Project of Novo Nordisk. T. Pieber was a paid consultant for Novo Nordisk, Eli Lilly, and Aventis, and is on the advisory board of Novo Nordisk. I. Rakovac received an educational grant from the Austrian Diabetes Association 2003, sponsored by Novo Nordisk and Aventis. The Research Group performed trials for all three major insulin-producing companies.     

Mechanism of disopyramide‐induced hypoglycaemia in a patient with Type 2 diabetes

Background Disopyramide, an antiarrhythmia drug, has been reported to cause hypoglycaemia. Pre‐existing factors that increase the concentration of the drug in the blood increase the risk of hypoglycaemia. Furthermore, other factors can also increase the risk of hypoglycaemia even when disopyramide levels are in the therapeutic range. It has been proposed that disopyramide‐induced hypoglycaemia is caused by inhibition of the pancreatic B‐cell K_ATP channels. Case report We report a case of severe disopyramide‐induced hypoglycaemia in a 62‐year‐old woman with Type 2 diabetes taking low‐dose glimepiride treatment. She had not experienced hypoglycaemia prior to the start of disopyramide therapy. No further hypoglycaemic episodes occurred following withdrawal of disopyramide therapy. Functional study Current recordings of K_ATP channels expressed in Xenopus oocytes showed that at their estimated therapeutic concentrations, disopyramide and glimepiride inhibited K_ATP channels by about 50–60%. However, when both drugs were applied together, K_ATP channels were almost completely closed (~95%). Such dramatic inhibition of K_ATP channels is sufficient to cause B‐cell membrane depolarization and stimulate insulin secretion. Conclusions Disopyramide therapy is not recommended for patients treated with K_ATP channel inhibitors.     

Prevalence of impaired awareness of hypoglycaemia in adults with Type 1 diabetes

Aims Impaired awareness of hypoglycaemia (IAH) is thought to affect approximately 25% of people with Type 1 diabetes. While this estimate was based on retrospective information from patients in several small studies performed several years ago, validated methods of assessment have not been used in a large hospital clinic-based population to ascertain the prevalence in the present era. Methods Five hundred and eighteen people with Type 1 diabetes were recruited by random selection over a 2-year period. Participants completed a questionnaire documenting baseline characteristics and assessment of their awareness status using the method described by Gold et al. The number of episodes of severe hypoglycaemia they had experienced in the preceding year was recorded retrospectively. Results IAH was present in 19.5% of the cohort. Compared to those with normal awareness of hypoglycaemia, those with IAH were significantly older [mean ± standard deviation (sd ); 39.3 ± 12.9 vs. 45.9 ± 13.5 years, P < 0.001], had a longer duration of diabetes [median (interquartile range) 14 (8–22) vs. 23 (14–32) years, P < 0.001], and had a six-fold higher frequency of severe hypoglycaemia in the previous year [0.38 ± 1.04 (25th–75th centile 0–0) vs. 2.36 ± 4.81 (25th–75th centile 0–2) episodes per person, P < 0.001]. Conclusions The present survey of a large hospital-based clinic population has confirmed that a significant proportion of people with Type 1 diabetes (19.5%) continue to have IAH. Despite improvements in insulin therapies, intensification of insulin regimens and innovative patient education, the prevalence of IAH remains high in Type 1 diabetes.     

Insulin pump therapy in children and adolescents: improvements in key parameters of diabetes management including quality of life.

AIMS: To determine the impact of insulin pump therapy (continuous subcutaneous insulin infusion) on key parameters of diabetes management including quality of life in children and adolescents with Type 1 diabetes mellitus (T1DM). METHODS: All patients started on insulin pump therapy were prospectively followed before and after institution of insulin pump therapy. Data collected included age, duration of diabetes, glycated haemoglobin levels (HbA1c), anthropometric data and episodes of severe hypoglycaemia defined as hypoglycaemia resulting in coma or convulsion. A subset of patients also completed the Diabetes Quality of Life Instrument (DQOL) and Self-Efficacy for Diabetes Scale (SED) questionnaires to assess quality of life. RESULTS: At the time of analysis, 100 patients had been managed with insulin pump therapy. The mean age when starting pump therapy was 12.5 (3.9-19.6) years. Duration of therapy ranged from 0.2 to 4.0 years (mean 1.4 years, median 1.5 years). HbA1c decreased from 8.3 +/- 0.1% prior to pump therapy to 7.8 +/- 0.1% (P < 0.0001). Episodes of severe hypoglycaemia decreased from 32.9 to 11.4 per 100 patient years. Components of quality of life measures showed improvement on pump treatment. BMI standard deviation scores (z scores) did not increase. CONCLUSIONS: Pump therapy is proving an effective means of insulin therapy in the young patient that shows promise to improve glycaemic control with a reduction in hypoglycaemia frequency. Quality of Life measures suggest that psychosocial outcomes may be improved.     

Metabolic control and risk of hypoglycaemia during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis

Aim: Aim of this study was to analyse clinical correlates of HbA1c, and of overall, nocturnal, and severe hypoglycaemia, through direct‐weighted regressions, as well as the effect of different insulin regimens and insulin analogues, through meta‐analysis. Methods: Appropriate methodology (PRISMA statement) was used. Sixty‐seven randomized studies, published as full papers were analysed to identify predictors of both HbA1c and hypoglycaemia; studies were included in a meta‐analysis to study the effect of different insulin regimens or insulin analogues on HbA1c and hypoglycaemia during the first year of insulin treatment in type 2 diabetes patients. Results: Final HbA1c, change of HbA1c, hypoglycaemia, nocturnal hypoglycaemia and severe hypoglycaemia were associated with intensity of treatment. Final HbA1c was higher with basal than with twice‐a‐day or prandial, and with twice‐a‐day than with prandial regimen, with opposite figures for hypoglycaemia. Within basal regimens, detemir and glargine were similar to NPH insulin on HbA1c, with less hypoglycaemia and nocturnal hypoglycaemia; within prandial regimens, new analogues were more effective than regular insulin on HbA1c, and induced less hypoglycaemia. The effect of glargine on HbA1c and on hypoglycaemia vanished with increasing number of insulin injections. Conclusion: Metabolic control and hypoglycaemia are associated with intensity of treatment. Basal regimens have a reduced effect on metabolic control, but are associated with lower frequency of hypoglycaemia. Newer analogues, short‐ and long‐acting, yield better control and less hypoglycaemia than older analogues.     

Substitution of night-time continuous subcutaneous insulin infusion therapy for bedtime NPH insulin in a multiple injection regimen improves counterregulatory hormonal responses and warning symptoms of hypoglycaemia in IDDM

Summary In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean ± SEM): 16.1 ± 3.1 vs 23.6 ± 3.3) episodes during the last 6 weeks of treatment, p = 0.03 (CSII vs NPH)) with maintenance of good glycaemic control (HbA_1c 7.2 ± 0.2 vs 7.1 ± 0.2 %, p = 0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study. [Diabetologia (1998) 41: 322–329] Received: 21 July 1997 and in revised form: 7 October 1997