Number Of Severe Hypoglycemic Episodes Research Articles

Fear of hypoglycemia and associated factors in hospitalized patients with type 2 diabetes: a cross‑sectional study

The present cross-sectional survey was performed to assess the prevalence and factors associated with fear of hypoglycemia (FoH) in hospitalized patients with type 2 diabetes (T2D). Between July and December 2020, 494 patients with T2D were evaluated via structured questionnaires containing sociodemographic information, clinical information, and the Fear of Hypoglycemia-15 scale (FH-15). Patients were divided into the FoH and non-FoH groups according to the FH-15 score. Univariate and multivariate logistic regression analyses were performed to determine factors associated with FoH. Variables with P values < 0.1 in the univariate model were included in the multivariate model. In this study, the prevalence of FoH was 17.4% (86/494). 247 (50.0%) patients experienced hypoglycemic episodes in the past year, and 15 (3.0%) patients experienced severe hypoglycemic episodes in the past year. The mean age was 60.04 ± 11.71 years old, and female patients accounted for 39.9% of the sample. The item with the highest average FH-15 scores was: how often are you afraid of having hypoglycemia while alone? Multivariate logistic regression analysis indicated that living alone (OR 2.48; 95% CI 1.20–5.14; P = 0.015), number of hypoglycemic episodes in the past year (OR 1.06; 95% CI 1.03–1.10; P < 0.001), number of severe hypoglycemic episodes in the past year (OR 2.61; 95% CI 1.20–5.69; P = 0.016), and duration of insulin use (OR 1.06; 95% CI 1.02–1.10; P = 0.006) were associated with FoH. The prevalence of FoH in hospitalized patients with T2D was high. FoH was associated with living alone, number of hypoglycemic episodes in the past year, number of severe hypoglycemic episodes in the past year, and duration of insulin use. These findings can contribute to early decision-making for preventing, identifying, and improving FoH in patients with T2D. In the future, interventions aimed at reducing FoH to improve the harmful effects of FoH are necessary, such as increasing diabetes-related knowledge and skills, increasing social support, reducing psychological fear, and minimizing risks for hypoglycemic episodes.

Decreased cognitive function is associated with preceding severe hypoglycemia and impaired blood glucose control in the elderly individuals with type 1 diabetes.

This investigation aimed to clarify the relationship between cognitive function and blood glucose control in the elderly individuals with type 1 diabetes. In total, 45 patients with type 1 diabetes, age 74.9 ± 6.7years, and HbA1c levels of 7.9 ± 0.9% were studied. Severe hypoglycemia occurred in 33% of patients, and the number of severe hypoglycemia episodes was 0.6 ± 1.2 in the past 5years before the time of the cognitive function tests. We analyzed clinical data and dementia scores on the Revised Hasegawa's Dementia Scale (HDS-R), Mini-Mental State Examination (MMSE), and Dementia Assessment Sheet for Community-based Integrated Care System, and 21 items (DASC-21). There was a significant correlation between HbA1c and HDS-R, MMSE, respectively. There was a significant correlation between the number of severe hypoglycemic episodes and HDS-R, MMSE, and DASC-21, respectively. When the group with experience of severe hypoglycemia was compared to the control group, HDS-R, MMSE, and DASC-21 were meaningfully different after adjusting for age modeling analysis of covariance. In elderly individuals with type 1 diabetes, our results suggest that high HbA1c for the past 5years from the cognitive function test and a history of severe hypoglycemic episodes from the time of disease diagnosis are related to decreased cognitive function.

Impaired awareness of hypoglycaemia in women with type 1 diabetes in pregnancy: Hypoglycaemia fear, glycaemic and pregnancy outcomes.

AimsTo examine maternal fear of hypoglycaemia, glycaemia and pregnancy outcomes in women with impaired and normal awareness of hypoglycaemia.MethodsA pre‐planned sub‐study of 214 pregnant women with type 1 diabetes who participated in the CONCEPTT trial. Participants completed hypoglycaemia fear surveys (HFS‐II) at baseline. Logistic regression and Poisson regression analyses were used to obtain an adjusted estimate for the rate ratio relating awareness to the number of severe hypoglycaemic episodes, and for several neonatal outcomes in relation to the total HFS‐II score. The role of continuous glucose monitoring (CGM) use was examined.ResultsOverall, 30% of participants reported impaired awareness of hypoglycaemia (n = 64). Women with impaired awareness of hypoglycaemia had more episodes of severe hypoglycaemia (mean 0.44 vs. 0.08, p < 0.001) (12–34 weeks gestation) and scored higher on the HFS‐II scale (43.7 vs. 36.0, p 0.008), indicating more fear of hypoglycaemia. They spent more time below range (CGM <3.5 mmol/L) and exhibited more glycaemic variability at 12 weeks gestation. Higher overall HFS‐II scores were associated with a higher risk of maternal severe hypoglycaemia episodes (Rate Ratio 1.78, 95% CI 1.39–2.27). Women with impaired awareness of hypoglycaemia had less maternal weight gain but there were no differences in neonatal outcomes between women with impaired awareness of hypoglycaemia and normal hypoglycaemia awareness. Higher HFS‐II scores were associated with more nephropathy (Odds Ratio 1.91, 95% CI 1.06–3.4). CGM use after 12 weeks was not associated with the number of episodes of severe hypoglycaemia (RR 0.75, 95% CI 0.49–1.15; p = 0.18).ConclusionsIn pregnant women with type 1 diabetes, impaired awareness of hypoglycaemia is associated with more maternal severe hypoglycaemia episodes and more fear of hypoglycaemia. Having impaired awareness of hypoglycaemia and/or fear of hypoglycaemia should alert clinicians to this increased risk. Reassuringly, there was no increase in adverse neonatal outcomes.

Severe Hypoglycemia Increases Dementia Risk and Related Mortality: A Nationwide, Population-based Cohort Study.

There are few studies focused on the relationship between hypoglycemia and new-onset dementia in patients with type 2 diabetes and no study regarding mortality of dementia after hypoglycemia. We investigated the effect of severe hypoglycemia on dementia subtypes and its relation to overall mortality in patients with type 2 diabetes. We evaluated incident dementia, including Alzheimer disease and vascular dementia, among health checkup participants aged 40 years or older in the National Health Insurance System in Korea from January 2009 to December 2015. Episodes of severe hypoglycemia were examined for 3 years before the date of the health checkup. Among 2 032 689 participants (1 172 271 men, 860 418 women), 14 443 (0.7%) experienced severe hypoglycemia, during a mean follow-up period of 6.9 ± 1.7 years. Individuals in the severe hypoglycemia group were more likely to be diagnosed with dementia compared to individuals without severe hypoglycemia (23.3% vs 7.3%; P < .001) and the overall incidence of Alzheimer disease was higher than vascular dementia. Dementia risk rose with increasing number of severe hypoglycemic episodes (1 episode [hazard ratio (HR) = 1.54; 95% CI, 1.48-1.60], 2 or more episodes [HR = 1.80; 95% CI, 1.66-1.94]). Overall mortality was higher in participants with dementia, but without severe hypoglycemia (HR = 2.03; 95% CI, 1.96-2.10) and severe hypoglycemia, but without dementia (HR = 4.24; 95% CI, 4.29-4.40), and risk of death was highest in those with both severe hypoglycemia and dementia (HR = 5.08; 95% CI, 4.83-5.35). Severe hypoglycemia is associated with dementia, especially Alzheimer disease and mortality; together, they have an additive effect on overall mortality.

Hypoglycemic Confidence in the Partners of Adults with Type 1 Diabetes.

Background: Hypoglycemic confidence (HC) represents the degree to which an individual feels secure regarding his or her ability to stay safe from hypoglycemia-related problems. Self-report scales assessing HC in adults with type 1 diabetes (T1D) have found that greater HC is associated with better glycemic control and that HC rises significantly after real-time continuous glucose monitoring is introduced. To determine whether HC might be similarly meaningful in the partners of T1D adults, we developed the Hypoglycemic Confidence Scale for Partners (Partner-HCS). This article describes the construction and validation of the Partner-HCS and examines how HC in T1D partners is related to hypoglycemia-related experience and key psychosocial constructs. Methods: Items were developed from interviews with seven T1D partners, resulting in 12 self-report items. Exploratory factor analysis (EFA) was then conducted on data collected from T1D partners (n = 218). Variables to establish construct validity for the Partner-HCS included partner-reported diabetes distress, hypoglycemic fear, generalized anxiety, and confidence regarding glucagon use, as well as frequency of recent severe hypoglycemia in the T1D adult. Hierarchical regression analyses examined the unique contribution of Partner-HCS scores, independent of hypoglycemic fear, to key psychosocial constructs and hypoglycemia-related factors. Results: EFA of the 12 items yielded a single-factor solution, accounting for 51.2% of the variance. Construct validity was demonstrated by significant univariate associations with key psychosocial constructs. Importantly, Partner-HCS total score was, independent of hypoglycemic fear, significantly associated with diabetes distress (P < 0.05), overall relationship satisfaction (P = 0.004), number of severe hypoglycemic episodes in the last 6 months (P < 0.05), and confidence using glucagon (P = 0.007). In total, 38.5% of T1D partners indicated relatively low HC. Conclusions: HC is an important facet of the experiences of T1D partners. It is related to, yet distinct from, hypoglycemic fear. The Partner-HCS is a reliable, valid method for assessing HC in partners of T1D adults.

Quality-of-life and treatment satisfaction in actual clinical practice of patients with Type 1 diabetes mellitus (T1DM) and hypoglycemia treated with insulin degludec

Objective: The frequency of hypoglycemia in patients with T1DM is high and results in a poorer quality-of-life and low treatment satisfaction. The aim of this study is to demonstrate the effect of changing the basal insulin (glargine or detemir) to insulin degludec.Methods: An observational analytical study was conducted on a cohort of 110 patients with T1DM. The patients were administered three questionnaires to assess treatment satisfaction (DTSQ-s), fear of hypoglycemia (HFS-II) and quality-of-life (EQ-5D), before the change and at 6 months. A statistical analysis was performed for repeated measures.Results: The 110 patients with T1DM had a mean diabetes duration of 19.1 (11.6) years, 53.6% were men, the mean age was 43.4 (15.4) years, and the mean BMI was 25.2 (4.2) kg/m2. After 6 months, there was a significant reduction in baseline fasting plasma glucose (from 159.1 [68.6] to 132.9 [56.6] mg/dL; p < .001) and HbA1c levels (from 7.82% [1.2] to 7.6% [1.2]; p = .002). A reduction in the number of severe hypoglycemic episodes (0.17 [0.5] vs 0.05 [0.2]; p = .03) was observed. At 6 months, an improvement in the DTSQ-s (from 24.3 [5.5] to 27.3 [5.4]; p < .001) was observed. There was a decrease in the mean number of perceived hypoglycemia (from 2.9 [1.4] to 2.3 [1.4]; p = .003) and hyperglycemia (from 3.5 [1.3] to 2.7 [1.4]; p < .001). There was also a decrease in the mean HFS-II score (from 24.1 [14.0] to 20.0 [13.0]; p < .001). There were no significant differences in the EQ-5D index (from 0.91 [0.14] to 0.89 [0.16]; p = .13). However, there was significant improvement in the EQ-5D as measured by VAS (from 70.5 [16.5] to 73.6 [14.4]; p = .04).Conclusions: The change to insulin degludec in patients with T1DM improved their metabolic control, increased their satisfaction with the insulin therapy, and offered them improved quality-of-life.

Pig islet xenotransplantation

The current article reviews the rationale, sources and preparation of pig islets for xenotransplantation, and presents current progress in solving the problems associated with establishing pig islet transplant as a clinical treatment for type 1 diabetes. Islet transplantation is an effective treatment option for type 1 diabetes, but the available supply of human pancreases is insufficient to meet the need and demand for obtaining islets. Pig islets provide a readily available source for islet transplantation, with trials in non-human primates demonstrating their potential to reverse diabetes. The risk of zoonosis can be reduced by designated pathogen-free breeding of the donor pigs, but porcine endogenous retroviruses (PERVs) that are integrated into the genome of all pigs are especially difficult to eliminate. However, clinical trials have demonstrated an absence of PERV transmission with a significant reduction in the number of severe hypoglycemic episodes and up to 30% reduction in exogenous insulin doses. A number of methods such as production of various transgenic pigs to better xenotransplantation efficiency and the encapsulation of islets to isolate them from the host immune system are currently being tested to overcome the xenograft immune rejection. Furthermore, ongoing research is also shedding light on factors such as the age and breed of the donor pig to determine the optimal islet quantity and function.

Influence of health locus of control and fear of hypoglycaemia on glycaemic control and treatment satisfaction in people with Type 1 diabetes on insulin pump therapy

To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion. People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]. We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P < 0.001). HFS-II scores did not differ between the two groups. Internal MHLC score was negatively associated with HbA1c (r = -0.15, P < 0.05) and positively associated with the number of mild and severe hypoglycaemic episodes (r = 0.16, P < 0.05 and r = 0.18, P < 0.001, respectively) and with DTSQ score (r = 0.17, P < 0.05). HFS-II score was negatively associated with DTSQ score (r = -0.18, P < 0.05) and positively with number of severe hypoglycaemic episodes (r = 0.16, P < 0.5). In adults with Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control.

Human islet transplantation

that achieves insulin-independent, constant normoglycemic state and avoidance of hypoglycemic episodes is the replacement of a patient’s islet of Langerhans either by pancreas transplantation or by isolated islet transplantation. The cost of this benefit, however, is the need for immunosupressive treatment of the recipient with all its potential risks. Currently, only vascularized pancreas transplantation can re-establish long-term normoglycemia however this has been associate with significant morbidity and mortality. Approximately 25.000 patients worldwide underwent this procedure and it has been shown to improve quality of life and even reverse some secondary complications of diabetes.4 Simultaneous pancreas and kidney transplantation are presently considered the standard of care for selected patients with type I diabetes with end-stage renal failure.5 Diabetes is a major burden to healthcare economies despite the use of exogenous insulin injections. Type I diabetes mellitus is a chronic metabolic disorder that currently afflicts 5 million individuals in the world. It results from auto-immune mediated destruction of insulin secreting beta cells in islet of Langerhans of the pancreas.1 Long-term studies strongly suggest that tight control of blood glucose achieved by conventional or intensive insulin treatment, self blood glucose monitoring, and patient education can significantly prevent developing and retard the progression of chronic complications of this disease.2 On the other hand, the cost of this benefit was a threefold increase in the number of severe hypoglycemic episodes, a significant increase of body weight and dietary and other lifestyle restrictions affecting the quality of life.3 The only treatment for Type I diabetes mellitus Human islet transplantation

Safety and Efficacy of Gliclazide as Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Trials

Objective and DesignGliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156)Data SourcesMedline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database.SelectionIncluded were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used.ResultsNineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (−0.13% (95%CI: −0.25, −0.02, I2 55%)). One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2%) in 1,152 gliclazide users and 22 events (1.8%) in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I2 77%)). Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes.ConclusionsThe methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective compared to other glucose lowering agents. None of the trials were designed for evaluating cardiovascular outcomes, which warrants attention in future randomized trials.

Hypoglycemia in the diabetic patient: the controversy in its study, in search of its implications

Hypoglycemia is one of the greatest limitations regarding the treatment of diabetes, as well as one of the most expensive. Its relevance goes beyond the episode itself or the rare sequel. The occurrence of hypoglycemia is frequently followed by treatment adjustments involving the glycemic target, which can result in long term diabetes complications. Its medium and long term consequences are not yet understood in light of recent studies, which have renewed fears regarding an increased cardiovascular risk with its occurrence. Controversy around its definition, as well as serious methodological limitations, led to disparities between the results of the multiple studies of incidence and costs. The low adhesion of a significant number of diabetic patients to glycemic self-monitoring during symptomatic episodes leads to diagnostic uncertainty and, occasionally, to a worsening of the glycemic control. The health-care based studies result in great underestimation of its incidence given the fact that many episodes are mild in nature, and some severe hypoglycemic episodes are treated by the patient's family or friends. Recent studies revealed that a significant number of severe hypoglycemic episodes treated by health-care professionals doesn't involve transportation to an Emergency Department. The same data suggest that the largest portion of the direct and indirect costs of diabetic hypoglycemia is related to the episodes that are treated at the Hospital, particularly if the patient is admitted in the ward. In the past decades a great investment has been made in the development of multiple strategies for the avoidance of hypoglycemia, namely the continuous blood glucose monitoring devices, as well as new drugs. In spite of the efforts, hypoglycemia remains as one of the most important problems in the treatment of diabetes.

Does severe hypoglycaemia influence microvascular complications in Type 1 diabetes? An analysis of the Diabetes Control and Complications Trial database

Severe hypoglycaemia may have a role in aggravating micro- and macrovascular disease in diabetes. Data from the Diabetes Control and Complication Trial have been reanalysed to ascertain whether the frequency of severe hypoglycaemia exerted an influence on the development and progression of retinopathy or nephropathy in people with Type 1 diabetes. Using binary longitudinal multiple logistic regression, HbA(1c) at study baseline, mean HbA(1c) throughout the study and the number of severe hypoglycaemic episodes during the trial were compared to examine the risk of development/progression of retinopathy and nephropathy. Average HbA(1c) during the study and/or HbA(1c) at baseline were independently predictive of retinopathy and nephropathy both in the intensively and the conventionally treated patients (all P ≤ 0.001). However, the number of hypoglycaemic episodes did not add to HbA(1c) in predicting retinopathy [odds ratio (95% CI) 0.99 (0.96-1.01), P = 0.51 in intensively treated patients, 0.94 (0.89-1.00), P = 0.05, conventional] or nephropathy [odds ratio (95% CI) 0.98 (0.95-1.01), P = 0.48 intensive, 1.03 (0.98-1.10), P = 0.17 conventional]. The frequency of exposure to severe hypoglycaemia did not predict a different risk of developing retinopathy or nephropathy in either treatment group of the Diabetes Control and Complications Trial at any given HbA(1c) .

Continuous Subcutaneous Insulin Infusion in Adult Type 1 Diabetes Mellitus: Data from a Registry at the University Medical Centre Ljubljana, Slovenia

To evaluate the treatment indications, effectiveness and adverse events of continuous subcutaneous insulin infusion (CSII) in adults with type 1 diabetes mellitus using data from a registry at the University Medical Centre Ljubljana, Ljubljana, Slovenia. The registry included patients with type 1 diabetes who had converted from multiple daily injection (MDI) to CSII. Patients with complete data sets covering a period of ≥3 years were included in the study (n=184). Complications, glycaemic control and insulin dose during CSII were compared with data obtained during MDI. CSII resulted in significant reductions in glycosyated haemoglobin level and total daily insulin dose. The mean number of severe hypoglycaemic episodes during CSII was 0.17 per patient per year. Treatment of adults with type 1 diabetes mellitus by CSII can improve glycaemic control and reduce insulin requirements compared with MDI, however patient selection, education and continuous care are important parts of this therapy.

Bénéfices de l’insulinothérapie par pompe chez les enfants diabétiques de type 1

The Diabetes Control and Complications Trial clearly demonstrated the benefits of blood glucose control, especially in children and adolescents, in the prevention of long-term complications of type 1 diabetes (T1D). This can be achieved with intensive insulin treatment with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII), also known as insulin pump. The aim of this study was to compare glycemic control of T1D children treated with either CSII or MDI. Thirty-eight T1D children treated with CSII were compared to 38 children treated with MDI, matched for age, gender, and duration of diabetes. Collected data, including daily doses of insulin in IU/kg/d, HbA1c levels, body mass index expressed in standard deviation/age, number of severe hypoglycemia episodes and of admissions related to T1D expressed in events/patient/year, were retrospectively collected every 3 months. There was no difference between the 2 groups at baseline. During the 3 years of follow-up, patients treated with CSII had lower daily doses of insulin (0.78 ± 0.19 vs. 0.87 ± 0.22 IU/kg/d, p<0.05), significantly lower levels of HbA1c (7.5 ± 0.6 vs. 8.0 ± 1.3 %, p<0.05), and a decreased number of admissions related to T1D (0.07 ± 0.14 vs. 0.17 ± 0.22 events/patient/year, p<0.05) than children treated with MDI. In contrast, body mass index and number of severe hypoglycemic episodes did not differ between the two groups. No diabetic ketoacidosis episode was recorded in either group. The results from this study suggest that treatment with CSII provided better metabolic control than treatment with MDI, in spite of lower daily doses of insulin and without increasing acute complications, in children with T1D.

Severe hypoglycemia predicts major adverse outcomes in diabetic patients undergoing glycemic control regimes.

Severe hypoglycemia predicts major adverse outcomes in diabetic patients undergoing glycemic control regimes.

Continuous blood glucose monitoring in diabetes treatment

Continuous glucose monitoring system (CGMS) is a developing technology in the field of diabetes treatment since it enables patients to effectively control and adjust their insulin therapy. Clinical trials have shown its efficacy in lowering HbAlc significantly especially in adults with type 1 diabetes and those with HbAlc >8%. Improvement is sustained for at least one year. Conflicting data exist for children. Most recent studies agree that the nearly daily use of CGMS is accompanied by significant lowering of HbA1c independent of age. However, the randomized clinical trials have shown that the use of CGMS does not reduce significantly the number of severe hypoglycemic episodes as it is expected, but recent data indicate that it reduces the time spent in hypoglycemia. Accuracy remains a key issue for CGMS, particularly in children and adolescents who may have increased variability of blood glucose. CGMS cost is another barrier to the everyday use since reimbursement of CGM is limited to a few countries only. This review will focus on the present status of the use of CGMS in type 1 diabetes (T1D) patients.

Effect of Antihyperglycemic Agents Added to Metformin and a Sulfonylurea on Glycemic Control and Weight Gain in Type 2 Diabetes: A Network Meta-analysis

Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea. To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea. MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases. Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A(1c) (HbA(1c)) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea. Primary end points were change in HbA(1c) level, change in weight, and frequency of severe hypoglycemia. Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA(1c) level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents. Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions. There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patient's clinical characteristics. Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacăo de Aperfeicoamento de Pessoal de Nível Superior.

Alexithymia is associated with glycaemic control of children with type 1 diabetes

Aim This study examined the respective contributions of the demographics, medical variables and alexithymia characteristics of young diabetics to their glycaemic control. The goal was to replicate the role of the ‘difficulty describing feelings’ factor of alexithymia in the prediction of poor glycaemic control as has been found in adult diabetic populations. Method The study included 45 type 1 diabetic children, aged 8–12 years (24 girls and 21 boys). Participants completed a sociodemographic questionnaire and provided medical information on their diabetes. HbA 1c values (glycated haemoglobin), and the number of severe hypoglycaemic episodes and hospitalizations for hyperglycaemia, were collected for the previous 12 months (3 months for severe hypoglycaemias). Alexithymia characteristics were measured by means of the Alexithymia Questionnaire for children. Results Hierarchical regression analyses confirmed that both demographic (marital status and parental education; P < 0.05) and medical (duration of diabetes and daily self-monitoring of blood glucose frequency; P < 0.01) variables are associated with HbA 1c levels. More important, one alexithymia factor (difficulty describing feelings) was found to be an additional predictor over and above the other variables ( P < 0.01), explaining an additional 12% of the total variance in HbA 1c levels. Conclusion Confirming results already observed in diabetic adults, the present findings show, for the first time, that children who have difficulties in expressing their feelings to others are more at risk of poor glycaemic control. In future, it will be useful to identify the diabetic young people who have such difficulties and to consider interventions designed specifically for them.

Hospital Glucose Control: Safe and Reliable Glycemic Control Using Enhanced Model Predictive Control Algorithm in Medical Intensive Care Unit Patients

The aim of this study was to investigate the performance of the enhanced Model Predictive Control (eMPC) algorithm for glycemic control in medical critically ill patients for the whole length of intensive care unit (ICU) stay. The trial was designed as a single-center, open, noncontrolled clinical investigation in a nine-bed medical ICU in a tertiary teaching hospital. In 20 patients, blood glucose (BG) was controlled with a laptop-based bedside version of the eMPC. Efficacy was assessed by percentage of time within the target range (4.4-6.1 mM; primary end point), mean BG, and BG sampling interval. Safety was assessed by the number of severe hypoglycemic episodes (<2.2 mM). Twenty patients (69 +/- 11 years old; body mass index, 27.4 +/- 4.5 kg/m(2); APACHE II, 25.5 +/- 5.2) were included for a period of 7.3 days (median; interquartile range, 4.4-10.2 days) in the study. Time within target range was 58.12 +/- 10.05% (mean +/- SD). For all patients with at least 7 days in the ICU, there was no statistically significant difference between the daily mean percentage of times in target range in respect of the averages. Mean arterial BG was 5.8 +/- 0.5 mM, insulin requirement was 101.3 +/- 50.7 IU/day, and mean carbohydrate intake (enteral and parenteral nutrition) was 176.4 +/- 61.9 g/day. Three hypoglycemic episodes occurred in three subjects, corresponding to a rate of 0.02 per treatment day. In our single-center, noncontrolled study the eMPC algorithm was a safe and reliable method to control BG in critically medical ICU patients for the whole length of ICU stay.

Improved glycemic control without an increase in severe hypoglycemic episodes in intensively treated patients with type 1 diabetes receiving morning, evening, or split dose insulin glargine

Objective: To see if insulin glargine improves glycemic control in a clinical setting. Research design and methods: A questionnaire and electronic database were used to assess glycemic parameters for 292 type 1 diabetic subjects taking ≥4 injections per day and receiving glargine as their only long-acting basal insulin for at least 6 months. Sixty-three subjects were taking glargine in the morning, 125 were taking glargine in the evening, and 104 were splitting the glargine dose between the morning and evening. Results: The mean (±S.D.) age and duration of diabetes were 32±10 years and 15.9±10.3 years, respectively. The mean (±S.E.M.) durations of treatment with glargine were 13.1±0.6 months, 12.2±0.4 months, and 14.3±0.5 months for the morning, evening, and split treatment groups, respectively ( P<0.01). The A1C values improved significantly from baseline for the evening and the split dosage groups or when all groups were combined. The mean basal insulin dose was significantly reduced at the end of the study in all the three groups from baseline with no change in the short-acting insulin dose. The number of severe hypoglycemic episodes decreased from 379 in the year prior to glargine treatment to 167 in the post-glargine year. The weight gain was significantly higher in the group that took the split glargine dose ( P<0.01). Conclusions: Similar or improved glycemic control was achieved by administering glargine in the morning, evening, or using a split dose without any further increase in severe hypoglycemic episodes. Splitting the glargine dose did not offer any advantages in glycemic control parameters.