Lecanicillium aphanocladii: snake venom phospholipases A2 and proteases as tools to prospect enzymatic inhibitors.

Natural enzyme inhibitors have been widely described in literature because of its pharmacological and cosmetic applications. Fungi found in caves represent a promising source of bioactive substances that are still little explored scientifically. Thus, the present work evaluated the presence of enzymatic modulators in a filtrate obtained from the cultivation of the cave fungus Lecanicillium aphanocladii (Family: Cordycipitaceae). Snake venoms from Bothrops alternatus and Bothrops atrox were used as an enzymatic source for the induction of the phospholipase, proteolytic, thrombolytic, cytotoxic and coagulant activities. Compounds present in the fungal filtrate inhibited 50, 23·8, 26·6, 50·9 and 52·5% of the proteolytic, phospholipase, haemolytic, thrombolytic and coagulant activities respectively. The filtrate was not cytotoxic on erythrocytes, but induced partial dissolution of thrombi. Fungal enzyme inhibitors that have low or no toxicity and can be obtained on a large scale and at low cost are relevant in the medical-scientific context. Therefore, the inhibition of phospholipases A2 and proteases observed in the present work highlights the potential of fungal metabolites for the development of drugs that can be used in the treatment of haemostasis and inflammation-related disorders. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, secondary metabolites synthesized by Lecanicillium aphanocladii, a fungus isolated from caves, demonstrated modulating action on proteases and phospholipases A2 present in snake venoms of the Bothrops genus, widely used as tools for the study of pathophysiology processes related to haemostasis and inflammation. The results suggest the possibility of future applications for these metabolites in the development of pharmaceuticals of medical-scientific interest.

Psychological distress, self-efficacy and glycemic control in type 2 diabetes.

AIM: To investigate the association of glycemic control with depression, anxiety, self-efficacy and other diabetes-specific psychological measures in a cohort of adult patients with type 2 diabetes (T2D) free of severe chronic diabetes-related complications. METHODS AND RESULTS: In 172 T2D outpatients consecutively recruited at the Diabetes Center of Verona City Hospital, we performed a standard medical assessment and completed the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI) and the Multidimensional Diabetes Questionnaire (MDQ) Age, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were (median [IQR]): 64.0 [58.0-69.0] years, 31.0 [28.0-34.4] kg/m2, and 7.3 [6.7-8.0] %, respectively. The overall prevalence of anxiety and depression was 14.5% and 18.6%, respectively. Higher levels of HbA1c were significantly (p < 0.001) associated with a number of MDQ dimensions, such as higher perceived interference with daily activities (Spearman's rho coefficient = 0.33), higher perceived diabetes severity (rho = 0.28) and lower self-efficacy (rho = -0.27), but not with depression or anxiety. These three variables were also independent predictors of higher HbA1c levels, when entered in a multivariable stepwise-forward regression model that also included age, BMI, diabetes duration and diabetes-specific social support as covariates. CONCLUSION: Lower self-efficacy and higher diabetes distress were closely associated with poorer glycemic control. No direct association between HbA1c and clinical psychological symptoms was detected. These results highlight that a number of diabetes-specific psychological variables may play a role amidst psychological distress and glycemic control. Further studies are needed to elucidate the relevance of diabetes distress and self-efficacy to the achievement of individual glycemic targets.

Cochlear, auditory brainstem responses in Type 1 diabetes: relationship with metabolic variables and diabetic complications.

AIMS: Few studies have analysed the presence of hearing abnormalities in diabetes. We assessed the presence of subclinical auditory alterations and their possible association with early vascular and neurological dysfunction in young adults with Type 1 diabetes of long duration. METHODS: Thirty-one patients with Type 1 diabetes (mean age 33 ± 2.3 years, disease duration 25.7 ± 4.2 years) and 10 healthy controls underwent pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) analyses. Associations with metabolic variables and chronic complications were explored. RESULTS: Compared with healthy controls, patients with diabetes had significantly higher mean hearing thresholds, although still within the normoacusic range. DPOAE intensities at medium frequencies (2.8-4 kHz) were significantly lower in patients with diabetes. In ABR, in addition to waves I, III and V, we observed the appearance of a visible wave IV in patients with diabetes compared with controls (prevalence 61% vs. 10%, P < 0.05), and its appearance was related to a prolonged I-V interval (4.40 ± 0.62 ms vs. 4.19 ± 0.58 ms, P < 0.05). Diastolic blood pressure was higher in people with abnormal DPOAE (P < 0.05), whereas systolic blood pressure correlated with wave V and interpeak I-V interval latencies. A trend towards an association between evidence of wave IV and the presence of somatic neuropathy or abnormal cardiovascular autonomic tests was observed. CONCLUSIONS: Young adults with long-term Type 1 diabetes have subclinical abnormalities in qualitative auditory perception, despite normal hearing thresholds, which might reflect neuropathic and/or vascular alterations.

Depression, anxiety, cognitive impairment and their association with clinical and demographic variables in people with type 2 diabetes: a 4-year prospective study.

OBJECTIVE: To investigate depression, anxiety and cognitive impairment and their associations with clinical and socio-demographic variables in type 2 diabetes. METHODS: The Zung Self-Rating Depression-Anxiety Scale and Mini-Mental State Examination (MMSE) were administered at baseline and after 4 years to 498 consecutive patients, 249 non-insulin treated (NIT) and 249 insulin treated (IT), aged 40-80 years. RESULTS: At baseline, IT patients were older, had longer disease duration, higher HbA1c and did more glucose monitoring (p < 0.001, all) but their depression scores were lower than among NIT (p = 0.006), with no differences for anxiety or MMSE. After 4 years, 72 patients were lost to the follow-up, of whom 18 had died. 41 NIT had switched to insulin and increased BMI (p = 0.004), blood pressure (p < 0.001), retinopathy severity (p = 0.03) and microalbuminuria (p = 0.0045), but did not change their scores for depression, anxiety or MMSE. The remaining 171 NIT improved fasting glucose (p = 0.006), total cholesterol (p < 0.0001), triglyceride (p = 0.0026) and HbA1c (p = 0.0006). Despite increased prevalence of microalbuminuria and retinopathy (p < 0.0001, both), depression (p = 0.04) and MMSE (p = 0.0007) improved. Foot ulcers (p = 0.03), retinopathy (p < 0001), microalbuminuria (p = 0.0047) and hypertension (p < 0.0001) increased in the remaining 214 IT patients, in whom depression (p = 0.0005) and anxiety (p < 0.0001) worsened while MMSE improved slightly (p = 0.0002). On multivariate analysis, depression was associated with being a woman and anxiety with diabetes duration and lower schooling, which also affected MMSE scores. CONCLUSIONS: Depression was associated with female gender and worsening complications but not modified by diabetes duration or switching to insulin therapy. Diabetes duration and lower schooling may affect anxiety and cognitive impairment.

Stage of change and motivation to healthy diet and habitual physical activity in type 2 diabetes.

Lifestyle changes to healthy diet (HD) and habitual physical activity (HPA) are recommended in type 2 diabetes mellitus (T2DM). Yet, for most people with diabetes, it may be difficult to start changing. We investigated the stage of change toward healthier lifestyles according to Prochaska's model, and the associated psychological factors in T2DM patients, as a prerequisite to improve strategies to implement behavior changes in the population. A total of 1,353 consecutive outpatients with T2DM attending 14 tertiary centers for diabetes treatment completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments to define the stage of change for HD and HPA, respectively. Logistic regression was used to determine the factors associated with stages that may hinder behavioral changes. A stage of change favoring progress to healthier behaviors was more common in the area of HD than in HPA, with higher scores in action and maintenance. Differences were observed in relation to gender, age and duration of disease. After adjustment for confounders, resistance to change toward HD was associated with higher body mass index (BMI) (odds ratio (OR) 1.05; 95 % confidence interval (CI) 1.02-1.08). Resistance to improve HPA also increased with BMI (OR 1.06; 95 % CI 1.03-1.10) and decreased with education level (OR 0.74; 95 % CI 0.64-0.92). Changing lifestyle, particularly in the area of HPA, is not perceived as an essential part of treatment by many subjects with T2DM. This evidence must be considered when planning behavioral programs, and specific interventions are needed to promote adherence to HPA.

Diagnosis of type 1 diabetes within the first five years of life influences quality of life and risk of severe hypoglycemia in adulthood.

Progressive adaptation to disease is paramount to improve quality of life (QoL) and other psychological dimensions in type 1 diabetes (T1DM). This study aimed at identifying possible correlations between QoL, locus of control (LoC) and clinical variables in patients with T1DM followed up for 16 years. Fifty-nine patients (27 women) with T1DM, part of a cohort of 112 followed since 1996, accepted to participate. Patients were divided into those in whom onset of T1DM had been during the first 5 years of life (n = 16) or later. They were also stratified into worsened, stable and improved, based on whether their HbA1c had increased/decreased by 1 percentage point between baseline and last follow-up visit. QoL was measured by the Diabetes Quality of Life questionnaire (DQOL), translated into Italian and re-validated. The LoC was measured by the Peyrot- and Rubin-specific questionnaire. Patients who developed T1DM before age 5 had a better total DQOL score than those who developed it later in life, mainly due to the satisfaction dimension and a tendency to decreased fatalism in adult age. All subjects whose HbA1c had worsened from baseline had had their diagnosis after age 5 and reported more frequent episodes of hypoglycemia. Onset of diabetes after age 5 and more frequent hypoglycemia was more likely in subjects with worsened HbA1c (ORs 7.6, p < 0.10 and 20.3, p < 0.01, respectively, from a multivariate logistic model with HbA1c, dichotomized in 'worsened' vs all others, as dependent variable). Onset of T1DM during the first 5 years of life may result in better QoL and less fatalism in the long term. Presumably, these patients have no memory of disease onset, which may reduce trauma and facilitate adaptation to managing life with diabetes.

Diabetes-specific variables associated with quality of life changes in young diabetic people: the type 1 diabetes Registry of Turin (Italy).

BACKGROUND AND AIMS: Type 1 diabetes (T1DM) affects young people during the most active years of their life. Our aim was to assess quality of life (QoL) and associated variables in a large cohort of adults with childhood-onset and adult-onset T1DM. METHODS: A cohort of adult patients (18 years and older) from the T1DM Registry of Turin, Italy, was recruited. Clinical characteristics and Diabetes QoL (DQOL) questionnaire were assessed by standardized procedures. RESULTS: 310 adults completed the questionnaire. Age and diabetes duration at assessment (mean ± SD) were 32.8 ± 7.3 years and 17.3 ± 6.3 years, respectively. DQOL and its subscores were in the lower quartiles of their distributions, indicating a good level of QoL. However, scores were significantly higher in females than in males, particularly for the subscale of diabetes-related worries. In multivariate analysis, lower QoL was independently associated with female sex (ß = 1.07, 95% CI 1.03-1.11, p = 0.003), higher age at onset (ß = 1.03, 1.00-1.05, p = 0.009), lower schooling (ß = 1.05, 1.00-1.09, p = 0.02), higher fasting plasma glucose (ß = 1.03, 1.01-1.05, p = 0.008), daily SMBG >4 (ß = 1.06, 1.01-1.10, p = 0.01), severe hypoglycemia over the last year (ß = 1.06, 1.01-1.11, p = 0.02), lower numbers of diabetologic visits (ß = 1.07, 1.01-1.13, p = 0.02) and hypertension (ß = 1.06, 1.02-1.10, p = 0.005). Autonomic neuropathy was associated with diabetes impact. Female sex (ß = 4.36, 2.43-7.83) and daily SMBG >4 (ß = 3.77, 1.72-8.30) were independently associated with worst level and CSII with better level (ß = 0.22, 0.07-0.68) of diabetes-related worries. CONCLUSIONS: The impact of T1DM on QoL may depend on demographic, metabolic control-related variables, presence of complications and insulin delivery modality.

A cross-sectional survey of depression, anxiety, and cognitive function in patients with type 2 diabetes.

To evaluate the prevalence of depression in outpatients with type 2 diabetes and its possible correlation with anxiety, cognitive function, and clinical variables. The Zung Self-Rating Depression and Anxiety Scales and the Mini-Mental-State Examination were administered to 249 non-insulin-treated (NIT) and 249 insulin-treated (IT) outpatients with type 2 diabetes, aged 40-80, in a cross-sectional survey. Compared with a reported prevalence of 6-13% in the general population, 104 (20.9%) patients had either a score indicative of depression or were on anti-depressant medication. Assuming that medication might modify the responses to questionnaires, the latter patients were excluded from further analysis. IT patients had higher age, known duration of diabetes, HbA1c, more foot ulcers, retinopathy, microalbuminuria and practised more self-monitoring of blood glucose (P < 0.01 all) but a slightly lower mean depression score (P = 0.004) and similar anxiety or cognitive function. At multivariate analysis, depression was associated with anxiety (P < 0.001), age (P < 0.001), gender (men having lower scores than women, P = 0.042), and insulin treatment, IT patients being less depressed than NIT (P < 0.001), but none of the clinical variables. Anxiety correlated with age (P < 0.001). The association between depression and anxiety became progressively weaker with increasing age. These data confirm increased prevalence of depression in a population of patients with type 2 diabetes who did not show impaired cognitive function. The lack of correlation with disease duration, metabolic control, and complications suggests that depression may not appear/worsen with diabetes and/or its complications but rather supports suggestions that it might predate both.

Carbohydrate counting improves coping ability and metabolic control in patients with Type 1 diabetes managed by Group Care.

BACKGROUND AND AIMS: To assess, in patients with Type 1 diabetes (T1DM), the effects of adding a carbohydrate counting programme (CCP) to continuing education by Group Care on coping ability, quality of life (QoL), knowledge of diabetes, and metabolic control. MATERIALS AND METHODS: Out of 56 patients with T1DM followed by Group Care, 27 were randomized to receive an 8-session CCP and 29 controls continued Group Care without a CCP. QoL, knowledge, and coping ability were assessed at baseline and after 30 months. Glycated hemoglobin (HbA1c), body weight, blood glucose, hypoglycemic episodes, and insulin dosages were checked every 3 months. RESULTS: QoL improved (p<0.0001) in both CCP (88.7 ± 9.2 vs 78.0 ± 9.9) and control patients (88.7 ± 12.5 vs 80.4 ± 11.7). At the end of study, patients on CCP had better scores in knowledge [difference 0.72 (95% CI 0.44; 0.99), p<0.0001] and the 3 coping areas [problem solving: 1.75 (1.2; 2.3), p<0.0001; social support seeking: -1.4 (-2.3; -0.48) p<0.005; avoidance: -1.59 (-2.6; -0.56), p<0.005] than controls. All variables showed a greater, although not statistically significant, improvement in patients with poor schooling. At 30 months, HbA1c was lower in the CCP patients than controls (7.2 ± 0.9 vs 7.9 ± 1.4), p<0.05. There were no changes in insulin dosage, hypoglycemic episodes or blood lipids. CONCLUSIONS: This study confirms that Group Care improves QoL in people with T1DM, but suggests that specific educational and psychological supports are needed to modify adaptation to the disease. The CCP we developed appears effective in promoting change, also in patients with poor schooling.

A study of central serotoninergic activity in healthy subjects and patients with Type 2 diabetes treated by traditional one-to-one care or Group Care.

AIM: Central serotoninergic activity may modulate glucose metabolism via neuroendocrine effectors. Group Care is a clinico-pedagogic intervention that improves metabolic control and quality of life in Type 2 diabetes through lifestyle modification and, possibly, central mechanisms. The hypothesis that central serotoninergic activity is modified in patients followed by Group Care was tested by measuring their hypothalamic- pituitary-adrenal response to citalopram, a selective serotonin reuptake inhibitor. METHODS AND SUBJECTS: Ten healthy controls and 17 non-obese, non-insulin-treated patients with Type 2 diabetes received, in random order, iv infusions of either 20 mg citalopram or saline. Nine patients had been longterm on Group Care and 8 had always been on traditional one-to-one care. Circulating glucose, insulin, ACTH, cortisol, DHEA, GH and PRL were measured every 15 min for 240 min. Differences between areas under the curves after citalopram and saline (Δ-AUC) were calculated. RESULTS: Citalopram stimulated ACTH and cortisol secretion in healthy subjects (p=0.026 and p=0.011, respectively) and patients on Group Care (p=0.056 and p=0.038) but not in patients on traditional care. In healthy subjects, basal glucose correlated with growth hormone Δ- AUC (r=0.820; p=0.004) and inversely with insulin Δ-AUC (r=-0.822; p=0.003). The former correlation was preserved in the patients (r=0.637; p=0.026). CONCLUSIONS: Diabetes may blunt the response of the hypothalamic-pituitary-adrenal axis to citalopram, but this is preserved in patients followed by a long-term intervention model that improves clinical as well as cognitive and emotional variables.

Sleep abnormalities in type 2 diabetes may be associated with glycemic control.

Sleep disturbances may be associated with impaired glucose metabolism. The aim of this study was to evaluate sleep duration and quality in relation to glycemic control in patients with type 2 diabetes. In a cross-sectional study, sleep duration and quality were assessed in 47 middle-aged patients with type 2 diabetes treated with oral agents and without sleep disturbing complications and 23 healthy control subjects similar by age, sex, body mass index, occupation and schooling. Sleep was recorded by wrist-actigraphy for three consecutive days under free-living conditions. Univariate analysis showed lower sleep maintenance (P = 0.002) and sleep efficiency (P = 0.005), and higher fragmentation index (P < 0.0001), total activity score (P = 0.05) and moving time (P < 0.0001) in patients with type 2 diabetes. After adjusting for age, gender and schooling, fragmentation index and moving time remained significantly higher in the patients with diabetes (P < 0.05, both). HbA1c correlated inversely with sleep efficiency (r = -0.29; P = 0.047) and positively with moving time (r = 0.31; P = 0.031). These findings suggest that type 2 diabetes is associated with sleep disruptions even in the absence of complications or obesity. The relevance of sleep abnormalities to metabolic control and possible strategies to improve sleep quality in type 2 diabetes deserve further investigation.

The locus of control in patients with Type 1 and Type 2 diabetes managed by individual and group care.

AIMS: The locus of control theory distinguishes people (internals) who attribute events in life to their own control, and those (externals) who attribute events to external circumstances. It is used to assess self-management behaviour in chronic illnesses. Group care is a model of systemic group education that improves lifestyle behaviour and quality of life in patients with Type 1 and Type 2 diabetes. This study investigated the locus of control in Type 1 and Type 2 diabetes and the possible differences between patients managed by group care and control subjects followed by traditional one-to-one care. METHODS: Cross-sectional administration of two questionnaires (one specific for diabetes and one generic for chronic diseases) to 83 patients followed for at least 5 years by group care (27 Type 1 and 56 Type 2) and 79 control subjects (28 Type 1 and 51 Type 2) of similar sex, age and diabetes duration. Both tools explore internal control of disease, the role of chance in changing it and reliance upon others (family, friends and health professionals). RESULTS: Patients with Type 1 diabetes had lower internal control, greater fatalistic attitudes and less trust in others. Patients with either type of diabetes receiving group care had higher internal control and lower fatalism; the higher trust in others in those with Type 1 diabetes was not statistically significant. The differences associated with group care were independent of sex, age and diabetes duration. CONCLUSIONS: Patients with Type 1 diabetes may have lower internal control, fatalism and reliance upon others than those with Type 2 diabetes. Receiving group care is associated with higher internal control, reduced fatalism and, in Type 1 diabetes, increased trust in others.

A randomised controlled clinical trial of nurse-, dietitian- and pedagogist-led Group Care for the management of Type 2 diabetes.

AIM: To verify if Group Care, a model to manage Type 2 diabetes (T2DM) by systemic continuing group education, can be administered by nurses and dieticians under pedagogic guidance, and improve metabolic control, quality of life, Locus of Control, and insulin resistance. MATERIAL AND SUBJECTS: Twenty-five patients with non-insulin-treated T2DM were randomized to Group Care and 24 to continued habitual individual care and education delivered by a diabetes specialist and pedagogist, respectively. Six nurses and 1 dietician received training by an accredited programme, a detailed operating manual and pedagogical supervision throughout the study. Follow-up was for 2 yr and included measurements of fasting blood glucose, glycated hemoglobin (HbA1c), body mass index, waist circumference, lipids, creatinine, blood pressure, serum insulin, homeostasis model assessment (HOMA) index of insulin resistance, health behaviors, quality of life, state and trait anxiety, and Locus of Control. RESULTS: One patient on Group Care and 3 controls dropped out. At the end of study, the patients on Group Care had lower HbA1c (7.6+/-0.8 vs 8.4+/-1.3, p<0.05), insulin (18.0+/-9.6 vs 24.3+/-13.7, p<0.001), HOMA index (6.9+/-5.4 vs 9.2+/-6.6, p<0.05), and fatalistic attitude (17.2+/-5.9 vs 24.9+/-4.2, p<0.001) and better quality of life (65.0+/-11.0 vs 78.4+/-19.6, p<0.001) than controls. CONCLUSIONS: Group Care delivered by trained nurses and dietitian is associated with better outcomes than those obtained by a medically and pedagogically qualified team. It may offer a model for health operators to re-organize clinical practice and for patients to improve lifestyle and strengthen the therapeutic alliance with their carers.

Perception of, and anxiety levels induced by, laser treatment in patients with sight-threatening diabetic retinopathy. A multicentre study.

AIMS: To investigate how laser treatment is perceived, in terms of anxiety and awareness, by diabetic patients attending four centres in Northern Italy with specific interest and expertise in diabetic retinopathy, where work settings and flow are organized differently. METHODS: The Hospital Anxiety and Depression Scale (HADS), Family Apgar-List of Threatening Experiences (FA-LTE), State-Trait Anxiety Inventories 1 and 2 (STAI-1 and STAI-2) questionnaires were completed by 259 patients, 131 waiting for laser treatment and 128 control subejcts awaiting non-intervention visits. Open questions were also asked on whether patients had ever heard the word 'laser' and whether they could describe laser treatment. RESULTS: High scores were detected by HADS, STAI-1 and STAI-2 among patients waiting for photocoagulation. Anxiety was greater in women and people with poor schooling. After controlling for centres, gender, previous laser treatment and schooling, HADS and STAI-1 remained significantly lower among persons waiting for non-intervention visits. Having received photocoagulation previously did not modify anxiety. Anxiety was lower in those centres where facilities and resources were more patient-oriented. Most patients could neither describe photocoagulation nor explain why they were about to receive it, but had a negative perception and some described it with words evoking cruelty and pain. CONCLUSIONS: These data suggest that laser treatment is experienced as an event that causes anxiety. Preoperative education and counselling may help to reduce fear and patients' avoidance of treatment.

Evaluation of the locus of control in patients with type 2 diabetes after long-term management by group care.

AIM: To investigate the locus of control in patients with type 2 diabetes followed by systemic group education (Group Care) and traditional one-to-one care. METHODS: In a post-hoc analysis, two questionnaires were administered to 56 patients who had been followed for 5-7 years by Group Care and 51 controls followed by individual care, similar by age, sex, diabetes duration, glycaemia, insulinaemia, weight and other clinical variables. Patients on Group Care had lower HbA1c (7.40 +/- 1.21%) than controls (7.99 +/- 1.48%), P = 0.027. The Peyrot and Rubin questionnaire, specific for diabetes, and the Wallston and Wallston questionnaire, more generic for chronic diseases, were administered. Both questionnaires explore 3 areas: internal control of disease, and the role of chance or powerful other people, including health operators, in changing the disease. RESULTS: Both questionnaires showed lower scores for chance in patients followed by Group Care (P < 0.001), while scores for powerful others did not differ from those of patients followed by traditional care. The Peyrot and Rubin tool showed increased Internal Control (P < 0.001) in the patients followed by Group Care. Multivariate analysis showed that the HOMA index of insulin resistance was inversely related to Internal Control (B = -0.144, P = 0.005) independently of BMI and HbA1c. CONCLUSION: Fatalistic attitudes were lower and internal control higher in patients with type 2 diabetes followed by Group Care. These changes may be related to insulin resistance, above and beyond the effects of body weight and metabolic control.

A 3-year prospective randomized controlled clinical trial of group care in type 1 diabetes.

BACKGROUND AND AIMS: We showed that continuing education can be embedded into routine diabetes care by seeing patients in small groups rather than individually. Group care was cost-effective in improving quality of life, knowledge of diabetes, health behaviours and clinical outcomes in people with type 2 diabetes. The aim of this study was to verify if group care can also be applied to type 1 diabetes. METHODS AND RESULTS: Randomized, controlled clinical trial comparing 31 patients managed by group care with 31 managed by traditional one-to-one care. A syllabus was built and later remodulated with the patients in a series of focus-group meetings. The primary end-point was changes in quality of life. Secondary end-points were: knowledge of diabetes, health behaviours, HbA1c and circulating lipids. Differential costs to the Italian National Health System and to the patients were also calculated. After 3 years, quality of life improved among patients on group care, along with knowledge and health behaviours (p<0.001, all). Knowledge added its effects to those of group care by independently influencing behaviours (p=0.004) while quality of life changed independently of either (p<0.001). Among controls, quality of life worsened (p<0.001) whereas knowledge and behaviours remained unchanged. HDL cholesterol increased among patients on group care (p=0.027) and total cholesterol decreased in the controls (p<0.05). HbA1c decreased, though not significantly, in both. Direct costs for group and one-to-one care were Euros 933.19 and Euros 697.10 per patient, respectively, giving a cost-effectiveness ratio of Euros 19.42 spent per point gained in the quality of life scale. CONCLUSIONS: Group care is applicable and also cost-effective in type 1 diabetes. It improves quality of life, knowledge and behaviours. Future programme adjustments should strive to impact more on metabolic control.

Pre-pubertal onset of type 1 diabetes and appearance of retinopathy.

OBJECTIVES: It was suggested that the years of diabetes preceding puberty may not contribute to the development of retinopathy but evidence for this is conflicting. To verify the influence of pre-pubertal diabetes, we compared the correlations between prevalence of retinopathy and diabetes duration in patients who developed type 1 diabetes before and after puberty. METHODS: Six hundred and twenty-eight patients with diabetes onset at age< or =29, on insulin treatment and aged< or =60 at the time of screening for retinopathy were considered retrospectively. Pre-pubertal age was defined as 0-12 in males and 0-11 in females. Two hundred patients had developed diabetes before puberty and 428 after puberty. Screening was by ophthalmoscopy + 35 mm photography or digital photography. RESULTS: Prevalence of retinopathy was lower among patients with pre-pubertal onset and diabetes durations 10-14 and 15-19 years (p=0.006 and p=0.003, respectively) but prevalence rates became similar after 20 yrs duration. CONCLUSION: That retinopathy is infrequent and mild during childhood, is probably due to the short duration of diabetes rather than a specific protective effect of pre-puberty. After 20 years' duration, however, the prevalence of retinopathy is no longer influenced by age at onset, suggesting that, in the longer term, pre-pubertal years do contribute to the onset of retinopathy.

ROMEO: rethink organization to improve education and outcomes.

AIMS: Scarcity of resources, expertise and evidence-based models have so far limited delivery of patient-centred diabetes education. We have developed and validated a group care approach that is applicable to everyday clinical practice and cost-effective in improving metabolic control, knowledge of diabetes, health behaviours, and quality of life in Type 2 diabetes. A clinical trial (ROMEO) was planned to evaluate applicability and reproducibility of group care in other outpatients facilities and assess its impact on a larger patient population. METHODS: Multicentre, randomized, controlled clinical trial of group vs. individual care in the routine management of Type 2 diabetes. Nine hundred patient aged < 80, with diabetes of > or =1 year known duration, treated by either diet alone or diet and oral agents, will be recruited in 15 centres and followed for 4 years. Training of physicians, nurses and dietitians included preparation of operating manual and videos, interactive sessions, and evaluation of local facilities and resources. PRIMARY MEASUREMENTS: 3-monthly HbA1c, fasting blood glucose, body weight, waist-hip ratio, yearly blood lipids, and bi-yearly assessment of knowledge of diabetes, health behaviours and quality of life. SECONDARY OUTCOMES: systolic and diastolic blood pressure, evaluation of ECG for ischaemia and QT interval, hypoglycaemic and anti-hypertensive medication and cardiovascular events. Analysis will be by intention-to-treat. DISCUSSION: If ROMEO confirms that group care can be successfully implemented in different clinics, a novel clinico-pedagogic tool will have been acquired to support patient-centred education, improve lifestyle and outcomes, support team work, enhance providers' attitudes and competencies and ameliorate diabetes care organization.