Core Standards of the EUBIROD Project. Defining a European Diabetes Data Dictionary for Clinical Audit and Healthcare Delivery.

BACKGROUND: A set of core diabetes indicators were identified in a clinical review of current evidence for the EUBIROD project. In order to allow accurate comparisons of diabetes indicators, a standardised currency for data storage and aggregation was required. We aimed to define a robust European data dictionary with appropriate clinical definitions that can be used to analyse diabetes outcomes and provide the foundation for data collection from existing electronic health records for diabetes. METHODS: Existing clinical datasets used by 15 partner institutions across Europe were collated and common data items analysed for consistency in terms of recording, data definition and units of measurement. Where necessary, data mappings and algorithms were specified in order to allow partners to meet the standard definitions. A series of descriptive elements were created to document metadata for each data item, including recording, consistency, completeness and quality. RESULTS: While datasets varied in terms of consistency, it was possible to create a common standard that could be used by all. The minimum dataset defined 53 data items that were classified according to their feasibility and validity. Mappings and standardised definitions were used to create an electronic directory for diabetes care, providing the foundation for the EUBIROD data analysis repository, also used to implement the diabetes registry and model of care for Cyprus. CONCLUSIONS: The development of data dictionaries and standards can be used to improve the quality and comparability of health information. A data dictionary has been developed to be compatible with other existing data sources for diabetes, within and beyond Europe.

Effect of war on glycemic control in type II diabetic patients.

OBJECTIVE: To determine the effect of war-related, protracted stress on glycemic control in type II diabetic patients. RESEARCH DESIGN AND METHODS: We examined 35 patients with type II diabetes as part of their routine control in October 1990. We reexamined them in October 1991, 3 mo after the war in Croatia began. We also administered a questionnaire to assess the patients' exposure to stress and changes in diet and exercise. RESULTS: The patients were exposed to considerable stressors. The wartime diet differed from the prewar diet. We found significant changes in total serum cholesterol and TG values (P < 0.01), but we observed no significant changes in body weight, FBG, postprandial blood glucose, and HbA1c values. Insulin and glibenclamide dosages did not change. CONCLUSIONS: We detected no significant impact of stress on glycemic control, probably because of differences in individual stress responsiveness. Changes in the lipid status probably were attributable to changes in dietary habits caused by specific circumstances.

Reduction of diffusion capacity for carbon monoxide in diabetic patients.

Diabetes can cause the development of pulmonary complications due to collagen and elastin changes, as well as microangiopathy. This study demonstrates the relationship between pulmonary complications and other chronic complications in diabetes. Twenty-seven patients with diabetes, aged 21 to 62 years, who had had the disease from 3 to 32 years, were included in this study. The protein excretion rate (PER) and the diffusion capacity of the lung for carbon monoxide (DLCO) were included as parameters of the severity of complications. PER was determined by the Biuret method. DLCO was measured by the single-breath method and was corrected by the measurement of alveolar volume (VA). The values of DLCO as corrected by VA (DLCO/VA) were included in the statistical evaluation of the results. The variables of age, duration of diabetes, and complication parameters were included in a multiple regression model with forward, stepwise selection to assess their value in predicting DLCO/VA. The variables were found to be significant predictors of DLCO/VA (R2 = 0.46, adjusted R2 = 0.32, p < 0.022). However, proteinuria was the only significant independent predictor of DLCO/VA. This finding indicates that both renal and pulmonary complications of diabetes share a similar microangiopathic background.

Effects of a fixed mixture of 25% insulin lispro and 75% NPL on plasma glucose during and after moderate physical exercise in patients with type 2 diabetes.

OBJECTIVE: To compare the plasma glucose (PG) response with a fixed mixture of 25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3 h before exercise, to human insulin 30/70 (30/70) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-seven patients were treated in a randomized, open-label, 8-week, two-period crossover study. Mix25 was injected 5 min before breakfast and dinner throughout the study, as was 30/70 on inpatient test days and on outpatient dose titration days. Following the 4-week outpatient phase, patients were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min, separated by 30 min rest, starting 3 h after a 339 kcal breakfast. RESULTS: The 2-h postprandial PG was significantly lower with Mix25 ((mean +/- SEM) 10.5 +/- 0.4 mmol/l vs 11.6 +/- 0.4 mmol/l; p = 0.016). Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 (-3.6 +/- 0.29 mmol/l vs -4.7 +/- 0.31 mmol/l; p = 0.001). The maximum decrease in PG over 6 h, after exercise onset, was significantly less with Mix25 (-4.3 +/- 0.4 mmol/l vs -5.9 +/- 0.4 mmol/l; p < 0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms) during the inpatient test was not different between treatments. During the outpatient phase, the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 (0.7 +/- 0.2 episodes/30 d vs 1.2 +/- 0.3 episodes/30 d; p = 0.042). CONCLUSIONS: Mix25 resulted in better postprandial PG control without an increase in exercise-induced hypoglycemia. The smaller decrease in PG during the postprandial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70, especially for patients in tight glycemic control.

Emotional adjustment and metabolic control in newly diagnosed diabetic persons.

Emotional reactions to diagnosis were examined in a random sample of newly detected diabetic patients (n = 71) and compared with the indicators of glycemic control in a one-year-follow-up period. The social and emotional factors subscale of the diabetes care profile was used to determine the subjectively experienced burden, negative feelings and positive coping abilities. The initial struggle against the disease indicated three characteristic emotional patterns. Feelings of being able to cope with the disease predominated in group 1 (n = 36), negative emotional reactions, but with the ability to cope were observed in group 2 (n = 17) and negative feelings combined with weak coping abilities in group 3 (n = 18). The long-term indicators of glycemic control were shown to be worst in group 3 and best in group 1. Subjective perception of the disease was not associated with sociodemographic variables, with the exception of perceived coping abilities which were better in more educated persons and those with more familial support.

Total plasma antioxidants in first-degree relatives of patients with insulin-dependent diabetes.

Insulin-dependent diabetes mellitus (IDDM) is a chronic disorder that results from autoimmune destruction of the pancreatic beta-cells. Recent evidence suggests that oxidative damage, resulting from both cytokine-induced production of toxic free radicals and low antioxidant capacity of the beta-cell plays a significant role in the pathogenesis of IDDM. Islet cell antibodies (ICA) have been the best validated marker of risk for the development of IDDM in predisposed individuals, i.e. first-degree relatives of patients with IDDM. We investigated the total plasma antioxidant status (TAS) in both ICA-positive and ICA-negative first-degree relatives of patients with IDDM, to assess the level of overall protection against oxidative damage. TAS was significantly lowered in ICA-positive when compared to both ICA-negative and healthy subjects (p < 0.001), while no significant difference was found in comparison to recently diagnosed patients with IDDM. TAS values were not significantly influenced by gender, age and smoking habits in all groups, as well as by ICA titers in the group of ICA-positive subjects. Results indicate that prediabetic condition, apart from well-established immunological and metabolic alterations, could be associated with biochemical changes revealing complex disturbances of the antioxidative defence system. Although TAS is a functional rather than specific marker, its measurement is likely to be a valuable tool for understanding the mechanisms of specific beta-cell injury.

Relationship between autonomic function, 24-h blood pressure, and albuminuria in normotensive, normoalbuminuric patients with Type 1 diabetes.

We performed a battery of cardiovascular reflex tests, 24-h ambulatory blood pressure (AMBP) and 24-h urinary albumin excretion (UAE) in 116 normoalbuminuric and normotensive patients with Type 1 diabetes. Tests of heart rate variation (HRV) included the coefficient of variation (CV) and the low-frequency (LF), mid-frequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (CV, mean circular resultant--MCR), Valsalva ratio, and maximum/minimum 30:15 ratio. Autonomic neuropathy, characterized as an abnormality of more than two tests, was found in 33 patients. Patients with neuropathy compared to those without neuropathy showed significantly higher mean day and night diastolic blood pressure (dBP), mean systolic night blood pressure (sBP), and mean day and night heart rate (HR). Mean night dBP was inversely related to MF, HF, and HRV during deep breathing; mean day dBP and mean night sBP to HF; mean night HR to CV at rest, MF, HF, HRV during deep breathing, 30:15 ratio; mean day HR to HF, HRV during deep breathing, Valsalva, and 30:15 ratio. Mean 24-h UAE was not significantly different in neuropathic than in nonneuropathic patients. UAE was inversely related to CV at rest and HF. In the stepwise multiple regression analysis, reduced MF, HF, HRV during deep breathing, and high levels of UAE and HbA1c were associated with high night dBP. Autonomic neuropathy is already present in normotensive Type 1 diabetic patients at the normoalbuminuric stage and related to BP and albuminuria.

Quality of life following a change in therapy for diabetes mellitus.

OBJECTIVE: The study objective was to evaluate and compare quality-of-life (QOL) parameters between patients with type 2 (non-insulin-dependent) diabetes mellitus who changed therapy from an oral hypoglycaemic agent (OHA) to insulin and those who remained on an OHA. DESIGN: The World Health Organization Quality of Life Questionnaire (WHOQOL) was used to assess quality of life among 2 groups of patients with type 2 diabetes mellitus at baseline and after a 2-month follow-up period. SETTING: The study was conducted in the outpatient department of the Vuk Vrhovac Clinic, a referral centre for registration, treatment and follow-up of patients with diabetes mellitus in Zagreb, Croatia. PARTICIPANTS AND INTERVENTIONS: 32 consecutively recruited patients with type 2 diabetes mellitus who were switched from an OHA to insulin therapy (group 1) were compared with 28 patients who remained on OHA (group 2) with respect to QOL issues. The patient groups were comparable in terms of gender, age, duration of disease, education and family status. However, patients in group 1 had glycosylated haemoglobin (HbA1c) values greater than 9.5% on average during a period of approximately 6 months, which was the criterion used for switching to insulin therapy. MAIN OUTCOME MEASURES AND RESULTS: At baseline, various QOL ratings were higher among patients in group 2 than group 1, indicating better quality of life with respect to overall quality of life (t = -2.31, p = 0.03), physical health (t = -2.36, p = 0.02), psychological state (t = -2.01, p = 0.05) and level of independence (t = -2.75, p = 0.001), while no differences were found between groups with respect to the social domain, personal beliefs and environmental QOL aspects. After the follow-up period, the groups were comparable in all QOL aspects other than overall quality of life (t = -2.18, p = 0.03) and level of independence (t = -3.49, p = 0.001), both of which remained higher for patients in group 2. No changes in QOL parameters were detected within group 2 from baseline to the end of the 2-month follow-up period, whereas patients in group 1 showed significant improvement in psychological QOL determinants (t = -2.14, p = 0.04). CONCLUSION: Results of the study indicate that introducing insulin therapy in patients with type 2 diabetes mellitus and sustained elevated HbA1c levels might positively affect their quality of life.

A pilot study of mitochondrial DNA point mutation A3243G in a sample of Croatian patients having type 2 diabetes mellitus associated with maternal inheritance.

In this work, patients having type 2 diabetes mellitus and diabetic mothers were tested for the presence of mitochondrial DNA point mutation A3243G. This mutation is associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), diabetes and deafness. Twenty-two diabetic persons were screened. DNA was isolated from peripheral blood lymphocytes and from swabs of oral mucosa. The mitochondrial DNA point mutation A3243G was detected using PCR-RFLP test. The mutation was detected in oral mucosal DNA of two patients (but not from lymphocyte DNA). One patient was a man with hearing and visual impairments and proteinuria; the other was a woman having proteinuria but no hearing impairment. The mutation was not detectable in oral mucosal DNA from the control persons: 20 diabetic patients having diabetic fathers and 22 healthy, nondiabetic volunteers. The incidence of mitochondrial DNA point mutation A3243G in this study of Croatian diabetic patients is in line with data in the literature.

Effect of war-induced prolonged stress on cortisol of persons with type II diabetes mellitus.

The study was designed to assess the impact of protracted, war-induced stress on cortisol levels and glycemic control in persons with Type II diabetes mellitus. A randomly selected sample of 44 displaced Type II diabetic persons was compared with a group of diabetic persons matched for sex, age, weight, duration of diabetes, and type of treatment who had not been forced to leave their homes. The self-reported stress, depression level, serum cortisol, fasting blood glucose, and glycosylated hemoglobin were compared. The two groups were found to be significantly different in scores for self-reported stress and depression level. Passive coping patterns prevailed in the displaced group. The serum cortisol levels correlated positively with self-reported stress, negatively with active coping patterns, and were significantly higher in the displaced persons group. No significant differences were found between the group on the variables measuring glycemic control. The results indicate that prolonged stress need not worsen glycemic control in Type II diabetic patients.

[New diagnostic criteria and classification of diabetes mellitus]. / Novi dijagnosticki kriteriji i klasifikacija secerne bolesti.

World Health Organisation (WHO) has recently proposed new diagnostic criteria and classification of diabetes mellitus. A major change in diagnostic criteria is lowering of diagnostic fasting plasma glucose level: level of 7.0 mM/L or more in two separate samples is sufficient for the diagnosis. Diagnostic criteria for plasma glucose in 120-min. of oral glucose tolerance test are unchanged. Newly recommended fasting level seems to correlate better with 120-min. value and to be a good marker of increased cardiovascular risk. The new classification describes impaired glucose regulation with two stages: impaired fasting glycaemia (plasma glucose of 6.1-7.0 mM/L) which is a new category and impaired glucose tolerance. Both subcategories are not real clinical entities, but markers of diabetic and cardiovascular risk. Diabetes mellitus, as a clinical entity, is separated in four classes: type 1, type 2, other specific types and gestational diabetes. Gestational diabetes includes any glucose intolerance in pregnancy. The Croatian Board for Diabetes Mellitus recommends acceptance of these criteria and classification for clinical use in the country and suggests that OGTT be performed for metabolic syndrome detection in cases of impaired fasting glycaemia.

[National organization of health care in diabetes based on the "Croatian model"]. / Nacionalna organizacija zdravstvene zastite dijabeticnih bolesnika "Hrvatski model".

This review article shows the development and organization of the "Croatian Model" of organization of health care for diabetic patients from Professor Vuk Vrhovac to this day, and its inclusion in the St. Vincent Declaration-a group of recommendations agreed upon in 1989 with the aim to decrease the morbidity and mortality of diabetes and its complications. The Model is organized on primary, secondary and terciary levels of health care. After the administrative changes of 1993, specialized health care for diabetic patients is delivered through County and Regional Centres for Diabetes and the Diabetes Reference Centre (the Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases), a scientific and educational institution and a WHO Collaborating Centre. Mention is made of the Croatian Diabetes Registry and statistical data on the morbidity (the prevalence of diabetes in Croatia is 2.37%) and mortality of diabetes mellitus and its complications, of organization of health care for diabetic patients, their medical treatment and care in Croatia.

[The diabetic foot. The Croatian model--national consensus (clinical recommendations for diagnosis, prevention and therapy)]. / Dijabeticko stopalo. Hrvatski model--nacionalno usuglaseno misljenje (klinicke preporuke za dijagnostiku, prevenciju i lijecenje).

Diabetic foot occurs due to the loss of protective sense and circulation disorder and a marked proneness to infections. Mechanical stress of bone growths frequently leads to ulcerations. The prevention and timely treatment of diabetic foot requires the participation of both patients and all health care levels. This consensus is given for the purpose of procedure standardization. Education is the basis of prevention and should be carried out with every patient suffering from diabetes mellitus and those with a sensory defect in particular. Appropriate footwear significantly contributes to prevention and treatment of ulcers. As regards the treatment, the necessity of surgical approach with a long term and often manifold antibiotic therapy should be pointed out. Infections are usually mixed. The deeper the ulceration, the more likely the infection with anaerobes and Gram-negative bacteria occurs in addition to Gram-positive ones which are normally present in surface lesions. Strict metabolic control is a precondition for successful treatment. In conclusion, diabetic foot is a major health problem which requires multidisciplinary approach with permanent patient education as its essential part, and a specific cooperation of all levels and different health care specialties.

Croatian guidelines for the pharmacotherapy of type 2 diabetes

INTRODUCTION: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. PARTICIPANTS: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. EVIDENCE: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. CONCLUSIONS: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes.

Depression in Croatian Type 2 diabetic patients: prevalence and risk factors. A Croatian survey from the European Depression in Diabetes (EDID) Research Consortium.

AIMS: To determine the prevalence rate of and risk factors for depression in Croatian Type 2 diabetic patients. METHODS: Depressive mood was examined in 384 randomly selected outpatients with Type 2 diabetes. Center for Epidemiological Studies Depression Scale (CES-D) and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) were used to identify depressive disturbances. The groups with CES-D > or = 16 and < 16 were compared with respect to demographic, psychological and clinical characteristics. Regression analysis was used to determine risk factors for depression. RESULTS: Of the examined patients, 22% had CES-D scores > or = 16, and in 33% of them clinical depression was confirmed by the psychiatric interview. Depressed patients compared with the non-depressed ones reported more diabetes-related problems and poorer well-being (t = 6.71, P < 0.001 and t = 11.98, P < 0.001, respectively). Multiple regression analysis indicated female gender, experienced support and the level of emotional well-being to predict depression (R = 0.74, F = 15.3, P < 0.001). CONCLUSIONS: The obtained data indicate that the prevalence rate in Croatian Type 2 diabetic patients is comparable to findings from other cultural settings. Depressive symptoms can be predicted by psychological rather than disease-related variables. Psychological care for diabetic patients may be necessary to prevent depressive symptomatology.

The application of insulin using the jet injector DG-77.

UNLABELLED: To avoid soreness and psychic stress following insulin injections by needle and syringe, the new jet injector DG-77 was used. It is a portable percutaneous pressure device with a spring, simple to operate which can be used to apply two different types of insulin. Thirty type 1 and type 2a diabetic patients participated in the study (10 females, 20 males). Insulin was applied using a needle and the DG-77 device in the same region of the body. A standardized questionnaire was compiled concerning simplicity of application, soreness, wish to possess the device and the possibility of acquiring it. The results obtained regarding the type of application were as follows: traditional way: glycemia: at 07(00)-8.5, 10(00)-10.5, 13(00)-7.4 mmol/l; insulinemia: at 07(00)-7.5, 10(00)-20.2, 13(00)-21.0 mU/l; jet injector: glycemia - at 07(00)-8.4, 10(00)-10.4, 13(00)-8.4 mmol/l; insulinemia: at 07(00)-2.8, 10(00)-12.3, 13(00)-20.0 mU/l, which was not statistically significant; for glycemia: at 10(00), t = 0.110, p greater than 0.05, at 13(00), t = 1.88, p greater than 0.05, and for insulinemia at 10(00), t = 0.82, p greater than 0.05, and at 13(00), t = 1.23, p greater than 0.05. IN CONCLUSION: 1) blood glucose and insulin control with the jet injector administration of insulin was equally successful as with the standard insulin application; 2) incidence of hematoma was not significant; 3) eighty-five percent of patients prefer the injector due to its simplicity of application, reduced soreness and would wish to possess the device.

Diabetes in time of armed conflict: the Croatian experience.

During the summer of 1991, armed conflict broke out in the Republic of Croatia. This resulted in many deaths and the displacement of many persons, with population loss in some communities and additional population burden in others. Registration of diabetic persons has been compulsory in Croatia since 1975 and from available statistics compiled by the Vuk Vrhovac Institute for Diabetes in Zagreb it was known that in 1991 there were 111,096 diabetic persons in Croatia, 16% requiring insulin, 46% treated with oral agents and 38% using dietary treatment only. This information helped to plan adequate supplies during the emergency. Contacts with international organizations and friends were of value in overcoming shortages, the most useful gifts being battery-operated blood glucose measuring devices. A study in Zagreb failed to demonstrate an association between the stress of displacement and metabolic control. Somewhat unexpectedly, diabetes and its complications did not present a major public health problem during the first 8 months of the armed conflict, but the long-term effects of these events remain to be seen.

War-induced prolonged stress and metabolic control in type 2 diabetic patients.

Sound evidence that psychological stress may significantly worsen metabolic control in diabetic patients in lacking. The stressful effects of war on glycaemia control have not been assessed as yet. A randomly selected sample of displaced Type 2 diabetic persons (N = 44) was compared to a matched group of diabetic persons who had not been forced to leave their homes. The self-reported stress, depression level, fasting and post-prandial blood glucose, glycosylated haemoglobin and serum lipids were compared. The two groups were found to be significantly different in scores for self-reported stress and depression levels (P < 0.001). The proportion of subjects belonging to the category of clinically significant depression was larger in the group of displaced persons (P < 0.001), as well as the proportion of extreme scores for self-reported stress (P < 0.001). No significant differences between the groups were found for variables measuring metabolic control (P > 0.05), except for the serum triglycerides which were found to be significantly higher in the group of displaced persons (P < 0.01). This is assumed to be the result of differences in nutrition. The results do not demonstrate an association between prolonged stress and glycaemic control in Type 2 diabetic patients. The variability of data measuring stress and depression level in two extreme groups with respect to HbA1c values suggests that individual factors which determine the response to stressors need to be explored.