Add-on treatment with intermediate-acting insulin versus sliding-scale insulin for patients with type 2 diabetes or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy: a randomized crossover study.

The aim of this study was to compare the effectiveness and safety of intermediate-acting insulin (IMI) titrated on body weight and glucocorticoid dose with that of short-acting sliding-scale insulin (SSI) in patients on recurrent high-dose glucocorticoid-containing chemotherapy. We enrolled 26 patients with type 2 diabetes mellitus or random blood glucose level >12 mmol/l in a previous cycle of chemotherapy in a randomized crossover study. In two consecutive cycles of glucocorticoid-containing chemotherapy, participants were treated with either IMI or SSI, as add-on to routine diabetes medication. We compared time spent in target range (3.9-10 mmol/l), measured by continuous glucose monitoring (CGM), and the occurrence of hypoglycaemia. IMI resulted in a higher proportion of glucose values within target range than SSI (34.4 vs 20.9%; p < 0.001). There were no severe or symptomatic hypoglycaemic events. Two participants in each group had a subclinical hypoglycaemia detected only by CGM. Once-daily IMI resulted in better glycaemic control than SSI in patients with glucocorticoid-induced hyperglycaemia during chemotherapy. Safety was not compromised as the incidence of hypoglycaemia was low and not different between both regimens.

Frequency of cancer events with saxagliptin in the SAVOR-TIMI 53 trial.

The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial randomized trial of 16,492 patients (placebo, n = 8212; saxagliptin, n = 8280) treated and followed for a median of 2.1 years afforded an opportunity to explore whether there was any association with cancer reported as a serious adverse event. At least one cancer event was reported by 688 patients (4.1%): 362 (4.3%) and 326 (3.8%) in the placebo and saxagliptin arms, respectively (p = 0.13). There were 59 (0.6%) deaths adjudicated as malignancy deaths with placebo and 53 (0.6%) with saxagliptin. Stratification by gender, age, race and ethnicity, diabetes duration, baseline glycated haemoglobin and pharmacotherapy did not show any clinically meaningful differences between the two study arms. The overall number of cancer events and malignancy-associated mortality rates were generally balanced between the placebo and saxagliptin groups, suggesting a null relationship with saxagliptin use over the median follow-up of 2.1 years. Multivariable modelling showed that male gender, dyslipidaemia and current smoking were independent predictors of cancer. These randomized data with adequate numbers of cancer cases are reassuring but limited, by the short follow-up in a trial not designed to test this hypothesis.

Factors that drive insulin-dosing decisions of diabetes care providers: a vignette-based study in the Netherlands.

AIM: To test how certain patient factors would influence the decision of Dutch care providers regarding insulin dose adjustments. We hypothesize that some of these decisions would diverge from recent evidence and consensus statements. METHODS: We developed narrative vignettes describing clinical scenarios of patients receiving basal insulin therapy. For each vignette, the respondents were asked to indicate whether they would advise a change in insulin dose. A total of 520 paper questionnaires were distributed among physicians and nurses in primary and secondary care in the Netherlands. Multivariate linear and logistic regression analyses were performed to identify factors associated with dosing decisions. RESULTS: A total of 190 (37%) questionnaires were returned. In cases of a severe rather than mild hypoglycaemic event, care providers were nearly five times more likely to decrease the dose (odds ratio 4.77, 95% CI 1.65-13.75). Care providers were six times more likely to increase the dose when the patient's current dose was low (30 units) rather than high (90 units) (odds ratio 6.38, 95% CI 3.04-13.37). The plasma glucose concentration during a hypoglycaemic event and a known history of cardiovascular disease did not influence the care providers' dosing decisions. CONCLUSION: Evidence regarding the optimum insulin titration is not always translated into clinical practice. When formulating guidelines, misconceptions should be identified and addressed.

Effects of sitagliptin on counter-regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double-blind placebo-controlled crossover study.

AIMS: To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes. METHODS: We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction. RESULTS: Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008]. CONCLUSIONS: Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia.

The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis.

Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin may experience hypoglycaemia. However, recent data regarding the incidence of hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to determine the proportion of patients with type 2 diabetes mellitus that experience hypoglycaemia when treated with sulfonylurea or insulin. We searched MEDLINE and EMBASE for randomized controlled trials that compared incretin-based drugs to sulfonylureas or insulin and assessed hypoglycaemia incidence in the latter therapies. Subgroup and meta-regression analyses were performed to study possible associations with potential risk factors for hypoglycaemia. Data of 25 studies were extracted, 22 for sulfonylurea and 3 for insulin. Hypoglycaemia with glucose ≤3.1 mmol/L or ≤2.8 mmol/L was experienced by 10.1% [95% confidence interval (CI) 7.3-13.8%] and 5.9% (95% CI 2.5-13.4%) of patients with any sulfonylurea treatment. Severe hypoglycaemia was experienced by 0.8% (95% CI 0.5-1.3%) of patients. Hypoglycaemia with glucose ≤3.1 mmol/L and severe hypoglycaemia occurred least frequently with gliclazide: in 1.4% (95% CI 0.8-2.4%) and 0.1% (95% CI 0-0.7%) of patients, respectively. None of the risk factors were significant in a stepwise multivariate meta-regression analysis. Too few studies had insulin as comparator, so these data could not be meta-analysed. The majority of patients with type 2 diabetes mellitus on sulfonylurea therapy in clinical trials remain free of any relevant hypoglycaemia. Gliclazide was associated with the lowest risk of hypoglycaemia. Because participants in randomized controlled trials differ from the general population, care should be taken when translating these data into clinical practice.

Cold-induced activity of brown adipose tissue in young lean men of South-Asian and European origin.

AIMS/HYPOTHESIS: South Asians have a disproportionately high risk of developing abdominal obesity, insulin resistance and type 2 diabetes. Brown adipose tissue (BAT) has been identified as a possible target to fight obesity and protect against metabolic disturbance. We explored whether lower BAT activity in South Asians compared with Europids may contribute to the high risk of metabolic disturbance. METHODS: We studied 20 healthy men (ten Europids/ten South Asians, BMI 19-25 kg/m(2), age 18-32 years). Following 2 h of cold exposure (16-18°C) after an overnight fast, (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography-computed tomography (CT) and (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission computed tomography-CT were performed to visualise metabolic BAT activity and sympathetic stimulation of BAT. Metabolic BAT activity was defined as maximal standardised uptake value (SUV(max)) of (18)F-FDG, and sympathetic stimulation of BAT as semiquantitative uptake value (SQUV) of (123)I-MIBG. We performed hyperinsulinaemic-euglycaemic clamps to assess insulin sensitivity. Spearman's correlations for SUV(max) of (18)F-FDG and both SQUV of (123)I-MIBG and insulin sensitivity were determined. RESULTS: The median (interquartile range) SUV(max) of (18)F-FDG in South Asians (7.5 [2.2-10.6] g/ml) was not different from the median SUV(max) obtained in Europids (4.5 [2.2-8.4] g/ml; p = 0.59). There was no correlation between BAT activity and insulin sensitivity. Correlations between SQUV of (123)I-MIBG and SUV(max) of (18)F-FDG were positive, both in the total population (ρ = 0.80, p < 0.001) and after stratification by ethnicity (Europids, ρ = 0.65, p = 0.04; South Asians, ρ = 0.83, p = 0.01). CONCLUSIONS/INTERPRETATION: This is the first study to prospectively investigate ethnic differences in metabolic BAT activity during cold exposure. We did not find differences in BAT activity between South Asians and Europids. Therefore, it seems unlikely that BAT plays an important role in the development of unfavourable metabolic profiles in South Asians.

The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.

Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gut microbiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gut microbiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans.

Safety of a web-based insulin titration system for patients with type 2 diabetes mellitus - pilot study.

The treatment of type 2 diabetes patients with insulin requires active dose titration to obtain optimal glycemic control. We developed a web-based decision support system to guide patients in performing the titration task autonomously, at their homes. The system is based on a clinically validated algorithm. The aim of this study was to test the safety of the system in a pilot implementation in clinical practice. Patients were blinded from the advice given by the system and instead received insulin dosing advice given by caregivers. At the end of the pilot, advice of the system were evaluated on safety by an expert panel. In this pilot study six patients used the web-based system at their home. In total, 48 advice were logged in the system resulting in eighteen deviating systems dosing advice as compared to the advice of the caregiver. Evaluation of the eighteen deviating systems advice lead to the detection of one unsafe advice indicating a need to extend the algorithm with an additional safety decision rule.

[Diabetes mellitus]. / Diabetes mellitus.

Currently there are over 740,000 patients with diabetes mellitus in the Netherlands, and this number will increase further in the coming years. Approximately 90% of patients has type 2 diabetes, a metabolic disorder that is often associated with obesity, hypertension and increased cholesterol levels. Treatment of diabetes mellitus is essential to reduce the risk of severe complications with irreversible organ damage in the long-term. Gingivitis and periodontitis are more common in patients with diabetes mellitus and are now also considered as complications of diabetes. Collaboration among healthcare professionals is important for effective diabetes care.

The association of physical inactivity with Type 2 diabetes among different ethnic groups.

AIMS: To study differences in the association between physical inactivity and Type 2 diabetes among subjects from different ethnic groups. METHODS: We analysed data on 508 Caucasian, 596 African-Surinamese and 339 Hindustani-Surinamese participants, aged 35-60 years, in the population-based, cross-sectional Surinamese in the Netherlands Study on Health and Ethnicity (SUNSET) study. Physical inactivity was defined as the lowest quartile of reported activity, measured with the validated Short Questionnaire to Assess Health-Enhancing Physical Activity. Type 2 diabetes was defined as fasting plasma glucose levels ≥7.0 mmol/l or self-reported diagnosis. RESULTS: Physical inactivity was associated with Type 2 diabetes (OR 1.63, 95% CI 1.12-2.38) in the total group after adjustment for sex, age, BMI, ethnicity, resting heart rate, hypertension, smoking, history of cardiovascular disease, having a first-degree relative with Type 2 diabetes and educational level. However, this association was only significant in Caucasians (OR 3.17, 95% CI 1.37-7.30). Moreover, it appeared stronger in Caucasians than in Hindustani-Surinamese (OR 1.43, 95% CI 0.78-2.63) and African-Surinamese (OR 1.13, 95% CI 0.58-2.19), although the P-value for interaction was not significant. CONCLUSIONS: Physical inactivity was associated with Type 2 diabetes in the total group after adjustment for multiple risk factors, but this association was only significant in Caucasians. Also, it appeared stronger in Caucasians than in Hindustani and African-Surinamese, but formal testing for interaction provided no further evidence. These findings confirm the importance of exercise, but suggest that potential health gain may differ between ethnic groups. However, it should be noted that, in general, promotion of physical activity in populations with an increased a priori risk of Type 2 diabetes, remains of the utmost importance.

Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial.

AIMS: To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. METHODS: In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with Type 1 diabetes (40 women) currently treated with multiple daily injections, age 18-65 years and HbA(1c) ≥ 8.2% (≥ 66 mmol/mol) to 26 weeks of treatment with either a sensor-augmented insulin pump (n = 44) (Paradigm(®) REAL-Time) or continued with multiple daily injections (n = 39). Change in HbA(1c) between baseline and 26 weeks, sensor-derived endpoints and patient-reported outcomes were assessed. RESULTS: The trial was completed by 43/44 (98%) patients in the sensor-augmented insulin pump group and 35/39 (90%) patients in the multiple daily injections group. Mean HbA(1c) at baseline and at 26 weeks changed from 8.46% (SD 0.95) (69 mmol/mol) to 7.23% (SD 0.65) (56 mmol/mol) in the sensor-augmented insulin pump group and from 8.59% (SD 0.82) (70 mmol/mol) to 8.46% (SD 1.04) (69 mmol/mol) in the multiple daily injections group. Mean difference in change in HbA(1c) after 26 weeks was -1.21% (95% confidence interval -1.52 to -0.90, P < 0.001) in favour of the sensor-augmented insulin pump group. This was achieved without an increase in percentage of time spent in hypoglycaemia: between-group difference 0.0% (95% confidence interval -1.6 to 1.7, P = 0.96). There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group (P = 0.21). Problem Areas in Diabetes and Diabetes Treatment Satisfaction Questionnaire scores improved in the sensor-augmented insulin pump group. CONCLUSIONS: Sensor augmented pump therapy effectively lowers HbA(1c) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections.

Reducing cardiovascular disease risk in patients with type 2 diabetes and concomitant macrovascular disease: can insulin be too much of a good thing?

Despite improvement of microvascular outcomes as a consequence of optimal glucose control in patients with type 2 diabetes, prevention of macrovascular complications is still a major challenge. Of interest, large-scale intervention studies (Action to Control Cardiovascular Risk in Diabetes, Action in Diabetes and Vascular Disease-Preterax and Diamicron Modified Release Controlled Evaluation and Veterans Affairs Diabetes Trial) comparing standard therapy versus more intensive glucose-lowering therapy failed to report beneficial impacts on macrovascular outcomes. Consequently, it is currently under debate whether the high doses of exogenous insulin that were administered in these trials to achieve strict target glucose levels could be responsible for these unexpected outcomes. Additionally, a potential role for plasma insulin levels in predicting macrovascular outcomes has emerged in patients with or without type 2 diabetes. These observations, combined with evidence from in vitro and animal experiments, suggest that insulin might have intrinsic atherogenic effects. In this review, we summarize clinical trials, population-based studies as well as data emerging from basic science experiments that point towards the hypothesis that the administration of high insulin doses might not be beneficial in patients with type 2 diabetes and established macrovascular disease.

Development of a web-based decision support system for insulin self-titration.

Insulin is the most potent agent for the treatment of diabetes mellitus. However insulin treatment requires frequent evaluation of blood glucose levels and adjustment of the insulin dose. This process is called titration. To guide patients with type 2 diabetes using once-daily long-acting insulin, we have developed a web-based decision support system for insulin self-titration. The purpose of this paper is to provide an overview of the phases of development and the final design of the system. We reviewed the literature, consulted an expert panel, and conducted interviews with patients to elicit system requirements. This revealed four important aspects: the insulin titration algorithm, the handling of hypoglycemic events, telemedicine functionalities, and visiting frequency monitoring. We used these requirements to develop a fully functional system.

The environment within: how gut microbiota may influence metabolism and body composition.

Obesity, diabetes and consequently atherosclerotic vascular disease have become major health and public health issues worldwide. The increasing and staggering prevalence of obesity might not only be explained by nutritional habits or the reduction of energy expenditure through decreased physical activity. In addition, recent studies have focused on intestinal microbiota as environmental factors that increase energy yield from diet, regulate peripheral metabolism and thereby increase body weight. Obesity is associated with substantial changes in composition and metabolic function of gut microbiota, but the pathophysiological processes driving this bidirectional relationship have not been fully elucidated. This review discusses the relationships between the following: composition of gut microbiota, energy extracted from diet, synthesis of gut hormones involved in energy homeostasis, production of butyrate and the regulation of fat storage.

Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes.

We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2 diabetes inadequately controlled on oral agents (including metformin) were randomized to insulin glargine or detemir. Secretagogues were stopped or maintained at the site-investigators' discretion. During the study, 57.6% of patients continued their secretagogue treatment. Compared with patients stopping secretagogues, those who continued experienced significantly more hypoglycaemia and weight gain. Insulin doses, however, were significantly lower: 0.6 ± 0.4 versus 0.8 ± 0.4 U/kg/day (p < 0.001). The difference between groups in mean HbA1c reduction was not statistically significant. In conclusion, in type 2 diabetic patients starting basal insulin analogue therapy, continuing both metformin and secretagogues results in more hypoglycaemia and weight gain and lower insulin doses than only maintaining metformin.

Management of post-splenectomy patients in the Netherlands.

After splenectomy, patients are at increased risk of sepsis with considerable mortality. The risk of sepsis can be reduced by immunising these patients and by prescribing antibiotic prophylaxis. The purpose of our study was to determine compliance with the international standards for the management of splenectomised patients in the Netherlands by investigating: (i) vaccination rates, (ii) the prescription of antibiotics and (iii) information in discharge letters. A retrospective review of the medical records and discharge correspondence of 609 splenectomy patients from 1997 to 2008 was performed. Data were collected from 28 hospitals. Adherence to vaccination guidelines and the prescription of antibiotics were assessed. It was found that 85.4% of post-splenectomy patients received pneumococcal vaccination, 39.4% received Haemophilus influenzae type B and 32.3% received meningococcal group C vaccination. Also, 12.4% of patients were discharged on prophylactic antibiotics. In less than 25% of cases were adequate recommendations regarding post-splenectomy management given to the general practitioner (GP). In the Netherlands, compliance with recommendations for the management of patients after splenectomy is insufficient. Fifteen percent of patients do not receive vaccination against pneumococci and the majority of patients do not receive antibiotic prophylaxis. The development and implementation of a national guideline for splenectomised patients is urgently required.

Assessment of splenic function.

Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell-Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, (99m)Tc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed.

Subjecting acute ischemic stroke patients to continuous tube feeding and an intensive computerized protocol establishes tight glycemic control.

INTRODUCTION: Tight glycemic control (TGC) after ischemic stroke may improve clinical outcome but previous studies failed to establish TGC, principally because of postprandial glucose surges. The aim of the present study was to investigate if safe, effective and feasible TGC can be achieved with continuous tube feeding and a computerized treatment protocol. METHODS: We subjected ten acute ischemic stroke patients with admission hyperglycemia (glucose >7.0 mmol/l (126.0 mg/dl)) to continuous tube feeding and a computerized intensive protocol with insulin adjustments every 1-2 h. Two groups of regularly fed patients from a previous study with a similar design served as controls. These groups comprised hyperglycemic patients treated according to an intermediate protocol with insulin adjustments at standard intervals (N = 13), and normoglycemic controls treated according to standard care (N = 15). The primary outcome was the percentage of time within target (4.4-6.1 mmol/l (79.2-109.8 mg/dl)). Secondary outcome was the number of patients with hypoglycemic episodes (glucose <3.0 mmol/l (54.0 mg/dl)). RESULTS: Median time within target was 55% in the continuously fed intensive group compared to 19% in the regularly fed intermediate group, and 58% in normoglycemic controls. Hypoglycemic episodes occurred in 20% of patients in the continuously fed group-lowest glucose level 2.4 mmol/l (43.2 mg/dl). In contrast, in the regularly fed group, this was 31%-lowest glucose level 1.6 mmol/l (28.8 mg/dl). CONCLUSIONS: TGC after acute ischemic stroke is feasible with continuous tube feeding and a computerized intensive treatment protocol. Although glycemic control is associated with hypoglycemia, no severe hypoglycemia occurred in the continuous tube feeding group.

Changing the glucose cut-off values that define hypoglycaemia has a major effect on reported frequencies of hypoglycaemia.

AIMS/HYPOTHESIS: The aim of this analysis was to quantify the relationship between the frequency of hypoglycaemia and various glucose cut-off points for the definition of hypoglycaemia, within a range of HbA(1c) strata. METHODS: Data from two trials examining insulin glargine dose titration in 12,837 type 2 diabetic participants starting insulin therapy were combined. Curves for hypoglycaemia frequency plotted against endpoint HbA(1c) level were constructed, using a range of glucose cut-off points for hypoglycaemia. RESULTS: During the 12-week study period, 3,912 patients recorded 21,592 hypoglycaemic episodes, comprising 242 severe, 8,871 symptomatic and 12,479 asymptomatic events, corresponding to hypoglycaemia event rates of 0.10, 3.8 and 5.3 events per patient year. Increasing the hypoglycaemia cut-off point from, for instance, <3.1 to <3.9 mmol/l more than doubled the percentage of affected patients, e.g. from 17.7 to 43.3% at HbA(1c) 7.0-7.2%. At higher hypoglycaemia cut-off points the proportion of patients having only asymptomatic hypoglycaemia increased, e.g. from 30.7% at <3.1 mmol/l to 61.7% of patients at a cut-off point of <3.9 mmol/l. In sensitivity analysis, 121 of 1,756 patients with at least one self-monitored blood glucose value <3.1 mmol/l experienced severe hypoglycaemia, compared with 149 of 3,912 patients with a self-monitored blood glucose level of <3.9 mmol/l. Thus, to identify 28 more patients with severe hypoglycaemia, the number of patients experiencing only non-severe hypoglycaemia more than doubled. CONCLUSIONS/INTERPRETATION: The glucose cut-off point defining hypoglycaemia greatly affects the reported frequency of hypoglycaemia. When hypoglycaemia is to be defined by a predetermined glucose level, to have clinical relevance the cut-off should be set at a lower level than the threshold of 3.9 mmol/l proposed by the American Diabetes Association.

Efficacy and safety of two 5 day insulin dosing regimens to achieve strict glycaemic control in patients with acute ischaemic stroke.

BACKGROUND: In patients with acute ischaemic stroke and hyperglycaemia, prolonged strict glycaemic control may improve clinical outcome. The question is how to achieve this prolonged strict glycaemic control. In this study, the efficacy and safety of two regimens with different basal to meal related insulin ratio are described. METHODS: 33 patients with ischaemic stroke and hyperglycaemia at admission were randomised in an open design to receive: (1) conventional glucose lowering therapy, (2) strict glucose control with predominantly basal insulin using intravenous insulin or (3) strict glucose control with predominantly meal related insulin using subcutaneous insulin in the first 5 days after stroke. The target range of glucose control for the last two groups was 4.4-6.1 mmol/l. 16 consecutive patients without hyperglycaemia at admission were included to serve as normoglycaemic controls. RESULTS: The median area under the curve (AUC) in the meal related insulin group was 386 mmol/l x 58 h (range 286-662) for days 2-5, and did not differ from the hyperglycaemic control group (median AUC 444 mmol/l x 58 h; range 388-620). There was also no difference in median AUC of the basal insulin group (453 mmol/l x 58 h, range 347-629) and the hyperglycaemic control group on days 2-5. In the first 12 hours, glucose profiles were lower in the groups treated with strict glucose control; median AUC was 90 mmol/l x 12 h (range 77-189) for the hyperglycaemic control group versus 81 mmol/l x 12 h (range 60-118) for the meal related insulin group (p = 0.03) and 74 mmol/l x 12 h (range 52-97) for the basal insulin group (p = 0.008). CONCLUSION: In intermittently fed ischaemic stroke patients, strict glycaemic control between day 2 and day 5 with two different basal bolus regimens did not result in lower glucose profiles due to postprandial hyperglycaemia. Continuous enteral feeding may therefore be needed to achieve prolonged strict glycaemic control in acute stroke patients.