Development and pharmacist-mediated use of tools for monitoring atypical antipsychotic-induced side effects related to blood glucose levels.

PURPOSE: Drug side effects often lead to serious outcomes. Administration of second-generation antipsychotics has resulted in diabetic ketoacidosis and diabetic coma leading to death. Therefore, pharmacists are required to collect information on clinical test values, determine the appropriate test timing, and coordinate with doctors for further clinical laboratory orders, all of which are labor-intensive and time-intensive tasks. In this study, we developed a side effect-monitoring tool and aimed to clarify the influence and efficiency of monitoring side effects by using the tool in patients taking atypical antipsychotics in whom it is necessary to check clinical test values such as blood sugar levels. METHODS: We extracted clinical test values for patients treated with second-generation antipsychotics from electronic medical records. The test values are automatically displayed in the side effect grade classification specified by CTCAE ver. 4.0. A database was constructed using scripts to provide alerts for the timing of clinical testing. The pharmacist used this tool to confirm clinical test values for patients taking medication and requested the physician to inspect orders based on the appropriate test timings. RESULTS: The management tool reduced the pharmacists' effort in collecting information on patients' prescription status and test values. It enabled patients to undergo tests at the appropriate time according to the progression of glucose metabolism and allowed for easy monitoring of side effects. CONCLUSIONS: The results suggested that regardless of pharmacists' experience or skill, the introduction of this tool enables centralization of side effect monitoring and can contribute to proper drug use.

Glycated hemoglobin A1c as a risk factor for severe hypoglycemia in pediatric type 1 diabetes.

OBJECTIVE: To assess the risk of severe hypoglycemia related to glycated hemoglobin A1c (HbA1c) levels in a population-based cohort of pediatric type 1 diabetes patients during two time periods since 1995. METHODS: The association between HbA1c levels and severe hypoglycemia (defined as requiring assistance from another person) or hypoglycemic coma (loss of consciousness or seizures) was analyzed by multivariable regression analysis in children and adolescents with type 1 diabetes from the DPV Diabetes Prospective Follow-up in Germany and Austria in 1995-2003 (n = 15 221 patients) and 2004-2012 (n = 22 318 patients). RESULTS: Mean adjusted rates of severe hypoglycemia and hypoglycemic coma decreased from 19.18 [95% confidence interval (CI), 17.95-20.48] and 4.36 (3.93-4.83) per 100 patient-years in 1995-2003 to 15.01 (14.18-15.88) and 2.15 (1.94-2.39) in 2004-2012, respectively (p < 0.001). From the first to the second period, the relative risk (RR) for severe hypoglycemia and hypoglycemic coma per 1% lower HbA1c decreased from 1.22 (1.15-1.30) to 1.06 (1.01-1.12) and from 1.27 (1.15-1.40) to 1.04 (0.94-1.16), respectively. Risk of severe hypoglycemia and coma declined most in patients with HbA1c levels of 6-6.9% (RR 0.70 and 0.43, respectively) and with HbA1c of 7-7.9% (RR 0.63 and 0.38, respectively). Mean HbA1c levels fell from 8.4% in 1995-2003 to 8.2% in 2004-2012, while the use of insulin pumps, short- and long-acting insulin analogs, and glucose monitoring increased (p < 0.001). CONCLUSIONS: In contrast to 1995-2003, low HbA1c has become a minor risk factor for severe hypoglycemia and coma in pediatric patients with type 1 diabetes in the 2004-2012 period.

Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study.

OBJECTIVE: Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study. RESEARCH DESIGN AND METHODS: Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables. RESULTS: The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6-32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5-17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9-55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI -10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2-42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1-25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine. CONCLUSIONS: There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice.

Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents.

OBJECTIVE: Earlier studies suggest that children with type 1 diabetes are more likely to have a subsequent diagnosis of celiac disease. However, research is sparse on the risk of subsequent type 1 diabetes in individuals with celiac disease. We sought to determine the risk of subsequent type 1 diabetes diagnosed before the age of 20 years in children and adolescents with celiac disease in a national, general population-based cohort. RESEARCH DESIGN AND METHODS: We identified 9,243 children with a diagnosis of celiac disease in the Swedish national inpatient register between 1964 and 2003. We then identified five reference individuals matched at time of diagnosis for age, calendar year, sex, and county (n = 45,680). Only individuals with >1 year of follow-up after study entry (diagnosis of celiac disease) were included in the analyses. RESULTS: Celiac disease was associated with a statistically significantly increased risk of subsequent type 1 diabetes before age 20 years (hazard ratio 2.4 [95% CI 1.9-3.0], P < 0.001). This risk increase was seen regardless of whether celiac disease was first diagnosed between 0 and 2 (2.2 [1.7-2.9], P < 0.001) or 3 and 20 (3.4 [1.9-6.1], P < 0.001) years of age. Individuals with prior celiac disease were also at increased risk of ketoacidosis or diabetic coma before the age of 20 years (2.3 [1.4-3.9], P = 0.001). CONCLUSIONS: Children with celiac disease are at increased risk of subsequent type 1 diabetes. This risk increase is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive.

Coma at the onset of young insulin-dependent diabetes in Japan. The results of a nationwide survey. Japan and Pittsburgh Childhood Diabetes Research Groups.

The descriptive epidemiology of diabetic coma at onset was investigated in a nationwide survey of insulin-dependent diabetic (IDDM) children (age at onset less than 18 yr) throughout Japan for the years 1970-81. Of the 1172 cases, 148 (12.6%) were unconscious at onset. Diabetic coma was highly associated with abnormalities in the biochemical variables. There was no sex difference in the frequency of coma; however, there was an inverse association with age wherein children under 5 yr of age were approximately two times more likely to present in coma than older children. There was a strong association with reported infections wherein patients with coma were more than twice as likely to report infection than patients without coma. It seemed that the frequency of coma did not decline during the study period. The risk of dying at onset was very high; diabetic children in coma (4.7%) were 12 times more likely to die than patients without coma.

Trends in hospital admissions among children aged 0-19 years with type I diabetes in The Netherlands.

OBJECTIVE: To determine the number and duration of hospital admissions due to diabetes in children aged 0-19 years between 1980-1991. RESEARCH DESIGN AND METHODS: Secondary analysis of data collected by the SIG Health Care Information was based on the 9th revision of the International Classification of Diseases. The subjects were all children in The Netherlands, aged 0-19 years. The main outcome measures were number and duration of hospital admissions due to type I diabetes (ICD 9 code 250.0-250.9). RESULTS: The hospital admission rate due to diabetes decreased > 30%. This decrease was statistically significant in all age subgroups. The total number of days in hospital due to diabetes decreased dramatically: from 24,961 in 1980 to 11,305 in 1991. The average duration of hospital stay length due to diabetes decreased as well from 14.5 days in 1980 to 11.9 days in 1991. CONCLUSIONS: The hospital admission rate and the length of hospital stay for diabetes in children aged 0-19 years have decreased, in spite of an increasing incidence. The hospital admission rate may decrease still further if more children with newly diagnosed diabetes can be adequately managed by team management at home in the initial phase.

Adverse events and their association with treatment regimens in the diabetes control and complications trial.

OBJECTIVE: To describe the incidence of adverse events associated with intensive versus conventional therapy of insulin-dependent diabetes mellitus (IDDM) as implemented in the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS: The DCCT was a randomized, controlled clinical trial conducted at 26 centers in the U.S. and 3 centers in Canada. All data were collected from patient notifications of events and/or standardized, quarterly interviews that were validated and analyzed at a data coordinating center as events per 100 patient-years. The 1,441 volunteers were between the ages of 13 and 39 with IDDM for 1-15 years. Average length of follow-up was 6.5 years (range 3-9). Subjects were randomly assigned to conventional or intensive diabetes treatment. RESULTS: The two treatment groups did not differ in mortality, major morbidity secondary to accidents, or ketoacidosis. However, intensive therapy was associated with a threefold increase in the risk of severe hypoglycemia (for hypoglycemia requiring assistance, the event rate per 100 patient-years was 61.2 in the intensive treatment group versus 18.7 in the conventional treatment group; for hypoglycemia involving coma or seizure, the rate was 16.3 vs. 5.4). Intensive therapy was also associated with a 73% higher risk of becoming overweight. There was a 46% reduction in the incidence of vaginitis in the intensive treatment group, but there were no significant differences in the rates of other infections. CONCLUSIONS: The major adverse effect of intensive therapy of IDDM is a threefold increase in the risk of severe hypoglycemia with potentially serious sequelae. An increased incidence of becoming overweight, the long-term significance of which has yet to be determined, was also observed. Because the results of the DCCT were attained in highly selected, healthy IDDM patients who received attentive clinical management and frequent health education, DCCT adverse event rates may not reflect incidence or prevalence rates that would be expected in nonselected populations or in other clinical settings.

A nationwide population-based study on the risk of coma, ketoacidosis and hypoglycemia in patients with celiac disease and type 1 diabetes.

AIMS: Celiac disease (CD) may influence metabolic control in type 1 diabetes (T1D). This work examines whether CD in T1D influences hospital admissions due to coma, ketoacidosis and hypoglycemia. METHODS: In population-based cohort study, individuals with CD were identified using biopsy data (1969-2008) from Sweden's 28 pathology departments. T1D was defined as a recorded diagnosis of T1D at age ≤30 years in the Swedish National Patient Register between 1964 and 2009. In total, 906 individuals had both T1D and CD and were matched for sex, age and calendar period with 4303 reference individuals. Through stratified Cox regression analysis, we modeled CD as a time-dependent covariate and estimated the risk of future coma, ketoacidosis and hypoglycemia, defined by relevant international classification of disease codes among T1D patients with and without CD. RESULTS: During follow-up, patients with both T1D and CD had 49 hospital admissions with diabetic coma, 91 episodes of ketoacidosis and 25 hypoglycemic events. Among patients with T1D, CD did not influence the risk of coma (adjusted HR 0.97; 95 % CI 0.72-1.32), ketoacidosis (adjusted HR 1.08; 95 % CI 0.86-1.34), or hypoglycemia (adjusted HR 1.34; 95 % CI 0.87-2.05). The absolute risk of coma was 621/100,000 person-years in T1D and CD (637 in controls). Corresponding figures for ketoacidosis were 1175/100,000 person-years in T1D and CD (1092 in controls) and for hypoglycemia 316/100,000 person-years (236 in controls). HRs for metabolic emergencies in T1D were similar in the first 5 years after T1D diagnosis as thereafter. CONCLUSIONS: Having a diagnosis of CD is unlikely to influence the risk of coma, ketoacidosis and hypoglycemia in T1D patients.

Accuracy of blood glucose meters for self-monitoring affects glucose control and hypoglycemia rate in children and adolescents with type 1 diabetes.

AIMS/HYPOTHESIS: This study investigated the accuracy of blood glucose meters for self-monitoring and its influence on glycated hemoglobin (HbA1c) levels and the frequency of hypoglycemic coma. MATERIALS AND METHODS: Self-measured and simultaneously obtained laboratory blood glucose values from 9,163 patients with type 1 diabetes <18 years of age in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by investigating their compliance with the International Organization for Standardization (ISO) criteria (versions 2003 and 2013) and by error grid analyses. Regression models elucidated effects on glucose control and hypoglycemia rates. RESULTS: Depending on the respective subgroup (defined by sex, age, duration of diabetes, mode of insulin therapy), 78.7-94.7% of the self-monitoring of blood glucose (SMBG) values met the old and 79.7-88.6% met the new ISO criteria. In Clarke and Parkes error grid analyses, the percentages of SMBG values in Zone A ranged between 92.8% and 94.6% (Clarke) and between 92.2% and 95.0% (Parkes). The patient group with SMBG devices measuring "far too low" (compared with the laboratory-obtained glucose levels) presented with a higher HbA1c level than those measuring "far too high," "too high," "identical/almost identical," or "too low" (based on quintiles of deviation). Performing "far too high" was associated with the highest rate of hypoglycemic coma in comparison with the other deviation quintiles. CONCLUSIONS: This study showed that current SMBG devices fulfilled neither the previous nor the new ISO criteria. Large deviations of the SMBG values from the "true" glucose levels resulted in higher HbA1c levels and markedly increased rates of hypoglycemic events.

Complications and prognosis of children with IDDM.

There was a marked reduction in the prevalence of complications in, and mortality status of, Japanese children with IDDM in the past 20 years. It is apparent that the improvement in medical treatment as well as social circumstance surrounding childhood diabetes in recent years contributed greatly to this change. However, when one compares Japanese data with those for Europe or the U.S., the present status is not yet satisfactory. In order to prevent the early development of diabetic complications followed by premature death associated with IDDM, an evenly distributed high-level medical system throughout Japan is required in addition to tight control of diabetes and patient education. Moreover, a population-based ongoing IDDM registry should be established from which risk factors for the progression of complications could be identified.

The adequacy of diabetic care for children in a developing country.

UNLABELLED: A cross-sectional study was conducted over 4 months evaluating the quality of care provided to diabetic children in public children's hospitals in Alexandria, Egypt. RESULTS: Adult diabetologists were the main healthcare providers (HCP) (60.4%) in the School Health Insurance Hospital followed by paediatric diabetologists in the University Hospital. Insured children had a significantly higher frequency of physical examination, investigations and diabetes education compared to uninsured children. One-quarter of insured and 22% of uninsured children were performing self monitoring of blood glucose, while 45.2% of insured children were checking glucosuria at home compared to 34.0% of uninsured children. Premixed suspensions of biosynthetic human insulin, administered mainly via a syringe, was the most commonly prescribed insulin type with little possibility for personal initiative. Acute diabetic complications were also higher in uninsured compared to insured children. The frequency of these life threatening acute diabetic complications in the school health insurance system is estimated to be approximately 12.7 severe hypoglycaemic and 57.2 hyperglycaemic/ketoacidotic episodes per 1000 diabetic children per year. Recurrence of diabetic emergencies was significantly higher among children of parents with lower educational levels and children living in semiurban and rural residence. Children with recurrent diabetic emergencies had lower educational achievement, and more grade repeating and school absence during the year. CONCLUSION: The results of this study appear to reflect marked deficiencies in the provision of information to children with diabetes and their parents in a developing country. A need for public-education strategies, consensus about treatment recommendations, use of more flexible insulin regimens, and devices for home monitoring is identified.

An epidemiological model for diabetes mellitus in the United States: five major complications.

Diabetes mellitus affects almost 5.5 million Americans each year. An estimated additional 5 million individuals may have diabetes, but remain undetected. Individuals with diabetes are at high risk for the development of micro- and macrovascular disease, diabetic coma and adverse outcome of pregnancy. The rate at which these complications develop are now partially identifiable for the United States. For 5 potentially preventable complications (retinopathy, adverse outcome of pregnancy, vascular disease, nephropathy and diabetic coma) the morbidity and mortality rates can now be calculated. There exist 50,000 cases of blindness due to diabetes with an additional 5800 new cases each year. Adverse outcome of diabetic pregnancy occurs in over 18,000 births each year, with as many as 4500 related perinatal deaths. Each year 40,000 diabetics are required to have a lower extremity amputation. Of the already 70,000 diabetics who have had an amputation, 25,000 will die this year. End stage renal disease affects 4000 diabetics each year. During the same time period, of the 7500 existing cases of end stage renal disease, 2000 will result in mortality cases. Diabetic coma (DKA and HHNK) accounts for 67,400 hospitalizations and results in 3600 deaths each year. Together these complications and those associated with cardiovascular disease account for 323,000 deaths with diabetes as the underlying or contributing cause in the United States.

Causes of death in Japanese diabetic patients examined by autopsy.

Autopsy records have been published annually by the Japan Society of Pathology. We collected diabetic autopsy cases from these records (1958-1985) and analysed the causes of death. Vascular diseases comprised 38-48% of all causes of death, malignant neoplasms 16-23% and infections 16-23%. Among vascular diseases, the incidence of coronary artery diseases has increased from 6.0 to 17%, but the frequency of nephropathy and cerebrovascular diseases has remained relatively stable since 1970. Diabetic coma and tuberculosis has decreased as a cause of death, while vascular diseases and malignant neoplasm have increased during these periods. These changes reflect the trend of changing disease structure in the general population, which is partly due to the changes in age distribution of the population.

[Complications of diabetes mellitus at the Hospital Center of Ouagadougou]. / Complications du diabète sucré au Centre hospitalier de Ouagadougou.

It is a four year study (1991 January to 1994 December) on four hundred diabetic people in Ouagadougou, aiming to assess the complications observed in these patients. The search of these complications have been systematic during the first consultation and during the follow-up through clinical examination and complementary exams. Most of classic complications have been found and can be split in two groups: 1) acute complications which included: metabolic ones observed on 17.5% of the patients (ketoacidosis 5%, hypoglycemia 11.2% and hyperosmolar coma 1.2%); infectious complications observed on 79% of the patients. The high frequency of these complications testifies of the difficulties of the management, under-information and insufficient education of the patients; 2) degenerative chronic complications including: microangiopathy: retinopathy (15.8%) and nephropathy (24.8%) which was complicated by chronic uremia in 9% cases; macroangiopathy in which: gangrene (7.5%), hypertension (20%), cardiac disease (8.7%), neurologic complications (35%) were the most frequent. These chronic complications accentuate mortality and morbidity linked to diabetes and increase the economical and social cost of this affection in a poor environment.

[Ketoacidosis in children and teenagers in Congo]. / Acidocétose chez l'enfant et l'adolescent au Congo.

Diabetes mellitus is frequent in African children and adolescents. Its treatment faces some problems and complications. Ketoacidosis is among the main complications and its prognosis is bad. This retrospective study reports 93 cases of young patients observed over 10 years. It aims at presenting the characteristics of ketoacidosis in Brazzaville. The results of this study have reported ketoacidosis in 79.3% of the cases. Stopping the treatment (48.1%) and infections (28.6%) were the main factors. In 18.3% of the cases, the disease started by ketoacidosis. Despite the high mortality rate (18.2%), a favourable evolution was observed in 83.3% of the cases. It is the first cause of death in children suffering Diabetes mellitus in the Department for diabetes mellitus and endocrine diseases at Brazzaville University Hospital. Health education of both parents and children, a qualified personnel should help reduce the frequency of this complication.