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.

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.

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.

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.

Perceptions of diabetic retinopathy and screening procedures among diabetic people.

AIMS: To assess how diabetic patients perceive retinopathy, screening for sight-threatening lesions and their own role in preventing blindness. METHODS: A questionnaire was administered to 258 consecutive patients after screening for retinopathy, according to the European Field Guide-Book procedure, in Turin (n = 130) and Wales (n = 128, W). All Welsh patients and 70 in Turin (T1) were on standard diabetes care at their clinic or general practitioner, whereas 60 in Turin (T2) were on permanent group education. RESULTS: According to 65%, 84% and 100% of patients in W, T1 and T2, respectively, diabetes may damage the eyes. Retinopathy had been heard of by 48% (W), 67% (T1) and 100% (T2). In T2, 82% of patients could give a meaningful description of retinopathy but only 17% could use correctly the word 'retina'. In W and T1, 16% and 19% could describe retinopathy but none could describe the retina. In W and T1, 47% and 57% believed they could not help with eye care, whereas 78% in T2 replied that they should control diabetes and 20% that eyes should be checked regularly. Regarding reasons for screening, 100% of patients in T2 answered 'prevention and checks', against 61% in T1 and only 9% in W. In T1 and W, 33% and 37% did not know why they were being screened. CONCLUSIONS: Patients' health perceptions and internal control mechanisms may be insufficiently developed for optimal participation in retinopathy screening. Diabetes care by long-term group education may address this problem.

Lifestyle intervention by group care prevents deterioration of Type II diabetes: a 4-year randomized controlled clinical trial.

AIMS/HYPOTHESIS: Metabolic control worsens progressively in Type II (non-insulin-dependent) diabetes mellitus despite intensified pharmacological treatment and lifestyle intervention, when these are implemented on a one-to-one basis. We compared traditional individual diabetes care with a model in which routine follow-up is managed by interactive group visits while individual consultations are reserved for emerging medical problems and yearly checks for complications. METHODS: A randomized controlled clinical trial of 56 patients with non-insulin-treated Type II diabetes managed by systemic group education and 56 control patients managed by individual consultations and education. RESULTS: Observation times were 51.2+/-2.1 months for group care and 51.2+/-1.8 for control subjects. Glycated haemoglobin increased in the control group but not in the group of patients ( p<0.001), in whom BMI decreased ( p<0.001) and HDL-cholesterol increased ( p<0.001). Quality of life, knowledge of diabetes and health behaviours improved with group care ( p<0.001, all) and worsened among the control patients ( p=0.004 to p<0.001). Dosage of hypoglycaemic agents decreased ( p<0.001) and retinopathy progressed less ( p<0.009) among the group care patients than the control subjects. Diastolic blood pressure ( p<0.001) and relative cardiovascular risk ( p<0.05) decreased from baseline in group patients and control patients alike. Over the study period, group care required 196 min and 756.54 US dollars per patient, compared with 150 min and 665.77 US dollars for the control patients, resulting in an additional 2.12 US dollars spent per point gained in the quality of life score. CONCLUSION/INTERPRETATION: Group care by systemic education is feasible in an ordinary diabetes clinic and cost-effective in preventing the deterioration of metabolic control and quality of life in Type II diabetes without increasing pharmacological treatment.

Group visits improve metabolic control in type 2 diabetes: a 2-year follow-up.

OBJECTIVE: To evaluate whether group visits, delivered as routine diabetes care and structured according to a systemic education approach, are more effective than individual consultations in improving metabolic control in non-insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized controlled clinical trial of 112 patients, 56 patients were allocated to groups of 9 or 10 individuals who participated in group consultations, and 56 patients (considered control subjects) underwent individual visits plus support education. All visits were scheduled every 3 months. RESULTS: After 2 years, HbA(1c) levels were lower in patients seen in groups than in control subjects (P < 0.002). Levels of HDL cholesterol had increased in patients seen in groups but had not increased in control subjects (P = 0.045). BMI (P = 0.06) and fasting triglyceride level (P = 0.053) were lower. Patients participating in group visits had improved knowledge of diabetes (P < 0.001) and quality of life (P < 0.001) and experienced more appropriate health behaviors (P < 0.001). Physicians spent less time seeing 9-10 patients as a group rather than individually, but patients had longer interaction with health care providers. CONCLUSIONS: Group consultations may improve metabolic control in the medium term by inducing more appropriate health behaviors. They are feasible in everyday clinical practice without increasing working hours.

Comparison of the cost-effectiveness of three approaches to screening for and treating sight-threatening diabetic retinopathy.

The purpose of this study was to analyse and compare the costs involved in screening for and treating sight-threatening diabetic retinopathy in three different clinical settings. In the first setting, diabetologists screened using ophthalmoscopy and color photography, according to the St. Vincent Declaration guidelines, and selected patients for further assessment by a visiting ophthalmologist and for treatment in another hospital. In the second setting, all patients were regularly referred to ophthalmologists, either in the same hospital or elsewhere, for all aspects of eye care. In the third setting, screening was done again with ophthalmoscopy alone by diabetologists who followed the St. Vincent Declaration guidelines; however, further assessment and treatment were carried out in the eye department of the same hospital. Costs to the Italian National Health Service and to patients were calculated per screening performed and per patient subjected to laser treatment as a result of screening. A sensitivity analysis was then performed to simulate the costs of standardised patient populations going through the three different settings. It is concluded that absolute costs would be lower, both for the Italian National Health Service and for patients, if screening, assessment and treatment were all carried out in the same hospital. Equipping a diabetic clinic specially for screening would not be more expensive than delegating eye care to external parties, even for a hospital without an eye department. Moreover, delegating eye care more than doubles costs for patients. Screening for, assessing and treating sight-threatening diabetic retinopathy may be a cost-effective procedure for society as a whole in Italy.

Diabetic retinopathy as a cause of blindness in the province of Turin, north-west Italy, in 1967-1991.

Diabetes is known to be a major contributor to blindness in industrialized countries but few data are available on the situation in Italy. As an introductory step to the implementation of permanent screening for diabetic retinopathy, a search was carried out on the causes of visual loss in the provincial territory surrounding Turin, the main city of North-West Italy. The case notes of all 4549 residents in the province who were certified blind between 1967 and 1991 were examined with regard to cause, age at onset, and year of onset of visual acuity < or = 1/20. Diabetic retinopathy was the second commonest cause of bilateral blindness (13.1% of cases), preceded by cataract (26.7%) and followed by myopia (11.1%), optic atrophy (8.9%), glaucoma (8.9%), retinitis pigmentosa (7.2%), and senile macular degeneration (4.1%). Diabetic retinopathy was the commonest eye disease among those who became blind between the ages of 50 and 70 and remained the leading cause of visual loss when the age groups 20 to 70 were pooled together. The incidence of diabetic retinopathy-related blindness did not show any trend to decrease over the 25 years investigated. It is concluded that, in spite of widespread availability of facilities for its assessment and treatment, diabetic retinopathy remains a leading cause of blindness in North-West Italy. This fully justifies the implementation of screening programmes and efficient referral chains for the early detection and prompt treatment of this complication of diabetes.

[Virilization in women. Clinical and therapeutic aspects]. / L'androgenizzazione nella donna. Aspetti clinici e terapeutici.

Androgenization in women can be divided, from a clinical standpoint, in two groups: a major form (with hirsutism, seborrhea, acne, hair loss, menstrual irregularities, masculinization of muscles and voice, mammary atrophy) and a minor one, with skin changes only (in particular hirsutism) with or without menstrual problems. The different clinical presentations are reviewed here: virilizing tumours of adrenal glands and ovaries, adrenogenital congenital syndromes, Cushing's syndrome and disease, iatrogenic forms, simple or idiopathic hirsutism, late onset enzymatic defects of adrenal steroidogenesis, polycystic ovary syndrome). The relevant therapeutic options are discussed. Special attention is devoted to the treatment of simple cutaneous androgenization, a problem affecting about 10% of women, by antiandrogenic drugs, mostly cyproterone acetate and spironolactone. These compounds compete with dehydrotestosterone for androgen cutaneous receptors, and have obtained good results, although not permanent. The indications, use and side-effects are also discussed.

The role of endothelium in the pathogenesis of diabetic microangiopathy.

Damage caused to the vessel wall by diverse mechanisms may lead to diabetic microangiopathy. Consequently, research work is more and more focusing on the pathophysiology of vascular cells, with particular emphasis on endothelium. This paper reviews the present knowledge on the alterations of small vessel endothelium in diabetes. The most important risk factors for diabetic microangiopathy are the duration of disease and the degree of metabolic control maintained throughout the years. However, genetic factors may also contribute. These are examined first, followed by the presumed roles played by increased protein glycation and the production of Advanced Glycosylation End Products, the "polyol pathway" and free radical generation. Endothelium is a widespread, extremely active organ which regulates complex physiologic functions and its structure and function are discussed in the second section of this review. The third part deals with how diabetes can affect endothelium and describes observations on endothelial metabolism in vitro as well as morphologic and functional alterations in the patients. Unfortunately, the mechanisms leading to progressive degeneration of the microcirculation and organ damage in diabetic patients remain largely unaccounted for.

Influence of gangliosides on primary and metastatic neoplastic growth in human and murine cells.

The influence of gangliosides on tumor growth and frequency of metastasis in vivo as well as on growth and motility of neoplastic cells in vitro was tested utilizing human and rodent cell populations. In mice receiving injections of a ganglioside mixture twice daily the tumor volume, the number of spontaneous metastases per animal, and the number of mice with metastasis was approximately double that of controls. Preincubation of neoplastic cells with the ganglioside mixture doubled the number of metastatic foci in the lungs of mice receiving the cells by i.v. injection. Addition of a ganglioside mixture to the culture medium enhanced motility of neoplastic cells about 3-fold. This finding was similar to that observed for capillary endothelium. The presence of gangliosides in the culture media for a 48-h incubation period about doubled the number of neoplastic cells as compared to controls; the same was observed for capillary endothelium. The data are interpreted to indicate that gangliosides improve growth and mobilization of capillary endothelium and neoplastic cells. Both events may concur in enhancing tumor growth in vivo, the first by improving angiogenesis, the second by direct action on the neoplastic cell population.

Levels of serum angiotensin-converting enzyme before and after forearm venous stasis in diabetic microangiopathy.

The levels of angiotensin-converting enzyme and Factor VIII-related antigen, 2 endothelial synthesized glycoproteins, were measured in basal conditions and after forearm venous stasis in 12 healthy controls and 12 patients with diabetic microangiopathy. Angiotensin-converting enzyme levels were similar in the controls and in the patients both basally (185 +/- 17 nm/ml/min (SEM) and 192 +/- 15, respectively) and after stasis (238 +/- 17 and 220 +/- 15), whereas Factor VIII-related antigen was lower in the former basally (101 +/- 13% vs 184 +/- 16%, p less than 0.001) and after stasis (140 +/- 21% and 243 +/- 21%, p less than 0.01). It is concluded that Factor VIII-related antigen is a more sensitive indicator of endothelial cell damage in diabetic microangiopathy than angiotensin-converting enzyme.

[Lactic acidosis]. / L'acidosi lattica.

Lactic acidosis is a metabolic disturbance characterized by an increase of the production/clearance ratio of lactate. Lactate is a catabolite of glycolysis when this takes place under anaerobic conditions. Clinically LA is characterized by: signs of acidosis, venous blood lactate greater than 5 mMol/l, arterial pH less than 7.25. LA is classified in type A, due to shock, and type B which, in turn, can be divided according to its pathogenesis in B1 correlated to particular pathologies, B2 due to exogenous substances and B3 caused by congenital metabolic diseases. LA is of particular interest in type II diabetes mellitus treated by phenformin. Current therapeutic directions, although suboptimal, are: to eliminate the causes of lactate hyperproduction by maintaining a sufficient efficiency of the cardio-vascular apparatus, to correct acidosis by using alkalinizing solutions, to remove pharmacologically or by dialysis the excess of lactate.