Diabetes and work: The need of a close collaboration between diabetologist and occupational physician.

AIM: The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. DATA SYNTHESIS: Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. CONCLUSIONS: Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.

Four-year impact of a continuous quality improvement effort implemented by a network of diabetes outpatient clinics: the AMD-Annals initiative.

AIMS: We evaluated the impact of a continuous quality improvement effort implemented by a network of Italian diabetes clinics operating in the national healthcare system. METHODS: This was a controlled before-and-after study involving 95 centres, of which 67 joined the initiative since 2004 (group A) and 18 were first involved in 2007 (group B, control). All centres used electronic medical record systems. Information on quality indicators was extracted for the period 2004-2007. Data were centrally analysed anonymously and results were published annually. Each centre's performance was ranked against the 'best performers'. We compared quality indicators between the two groups of centres over 4 years. RESULTS: Over 100 000 Type 2 diabetes mellitus patients were evaluated annually. The proportion of patients with glycated haemoglobin levels < 7% increased by 6% in group A (2007-2004 difference) and by 1.3% in group B. The proportion of patients with low-density lipoprotein-cholesterol < 100 mg/dl improved by over 10% in both groups. The rate of patients with blood pressure values < or = 130/85 mmHg increased in group A (+6.4%), but not in group B (-1.4%). The use of insulin increased in group A only (+5.2%), while the use of statins increased by over 20% in both groups. CONCLUSIONS: A physician-led quality improvement effort, based on the systematic evaluation of routine data, is effective in improving the performance of a large number of diabetes clinics. The small percentage increase in the number of patients at target, if applied to large numbers of patients, would translate into a significant impact on public health.

Obesity and changes in urine albumin/creatinine ratio in patients with type 2 diabetes: the DEMAND study.

BACKGROUND AND AIMS: Obesity is a potential risk factor for renal disease in non-diabetic subjects. It remains unclear whether this also applies to diabetic patients. We investigated whether obesity predicted changes in albumin excretion rate in individuals with type 2 diabetes. METHODS AND RESULTS: Fifty Italian diabetes outpatient clinics enrolled a random sample of 1289 patients. A morning spot urine sample was collected to determine urinary albumin/creatinine ratio (ACR) at baseline and after 1 year from the study initiation. Progression of albumin excretion was defined as a doubling in ACR, while regression was defined as a 50% reduction. Multivariate logistic regression analyses were used to evaluate correlates of these outcomes. Data are expressed as odds ratios (OR) with 95% confidence intervals (CI). The risk of progression increased by 7% (OR=1.07; 95%CI 1.00-1.15) for every 5-cm increase in waist circumference measured at baseline, and by 17% (OR=1.17; 95%CI 1.03-1.33) for every one-unit increase in BMI during follow-up. The likelihood of regression was not independently associated with any of the variables investigated. The effect of obesity on progression of ACR was independent of metabolic control, blood pressure, treatment, and baseline level of albumin excretion. CONCLUSIONS: We found a tight link between obesity and changes in albumin excretion in diabetic subjects, suggesting potential benefits of interventions on body weight on end-organ renal damage.

Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study.

AIMS: To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. METHODS: People with type 2 diabetes treated in out-patient settings aged 18-65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of 'upset') between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. RESULTS: In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. CONCLUSION: This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.

In Type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine.

AIMS: The superiority of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) with glargine is uncertain. In this randomized cross-over study, we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII. The primary end-point was glucose variability. METHODS: Thirty-nine patients [38.1 +/- 9.3 years old (mean +/- sd), diabetes duration 16.6 +/- 8.2 years, glycated haemoglobin (HbA(1c)) 7.6 +/- 0.8%], already on CSII for at least 6 months, were randomly assigned to CSII with lispro or MDI with lispro and glargine. After 4 months they were switched to the alternative treatment. During the last month of each treatment blood glucose variability was analysed using glucose standard deviation, mean amplitude of glycaemic excursions (MAGE), lability index and average daily risk range (ADRR). As secondary end-points we analysed blood glucose profile, HbA(1c), number of episodes of hypo- and hyperglycaemia, lipid profile, free fatty acids (FFA), growth hormone and treatment satisfaction. RESULTS: During CSII, glucose variability was 5-12% lower than during MDI with glargine. The difference was significant only before breakfast considering glucose standard deviation (P = 0.011), significant overall using MAGE (P = 0.016) and lability index (P = 0.005) and not significant using ADRR. Although HbA(1c) was similar during both treatments, during CSII blood glucose levels were significantly lower, hyperglycaemic episodes were fewer, daily insulin dose was less, FFA were lower and treatment satisfaction was greater than during MDI with glargine. The frequency of hypoglycaemic episodes was similar during both treatments. CONCLUSIONS: During CSII, glucose variability is lower, glycaemic control better and treatment satisfaction higher than during MDI with glargine.

Structural alterations in subcutaneous small arteries of normotensive and hypertensive patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: It is not presently known whether non-insulin-dependent diabetes mellitus (NIDDM) is associated with the presence of structural alterations in small arteries or whether the combination of hypertension and NIDDM may have an additive effect on endothelial dysfunction. Therefore, we investigated subcutaneous small arteries in 12 normotensive subjects (NT group), 18 patients with essential hypertension (EH group), 13 patients with NIDDM, and 11 patients with NIDDM and EH (NIDDM+EH group). METHODS AND RESULTS: Subcutaneous small arteries were evaluated by a micromyographic technique. The internal diameter, the media-to-lumen ratio, remodeling and growth indices, and the collagen-to-elastin ratio were calculated. Concentration-response curves to acetylcholine, bradykinin, the endothelium-independent vasodilator sodium nitroprusside, and endothelin-1 were performed. The media-to-lumen ratio was higher in the EH, NIDDM, and NIDDM+EH groups compared with the NT group. EH patients showed the presence of eutrophic remodeling, whereas NIDDM and NIDDM+EH patients showed 40% to 46% cell growth. The collagen-to-elastin ratio was significantly increased in the EH and NIDDM+EH groups compared with the NT group. The vasodilatation to acetylcholine and bradykinin was similarly reduced in EH, NIDDM, and NIDDM+EH groups compared with the NT group. The contractile responses to endothelin-1 were similarly reduced in EH, NIDDM, and NIDDM+EH patients. CONCLUSIONS: Our data suggest that the effects of NIDDM and EH on small artery morphology are quantitatively similar but qualitatively different and that the presence of hypertension in diabetic patients has little additive effect on small artery morphology and none on endothelial dysfunction.

Endothelial dysfunction in small resistance arteries of patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: Arterial hypertension is frequently associated with the presence of endothelial dysfunction in human subcutaneous small resistance arteries, as evaluated by responses to acetylcholine or bradykinin; however it is not known whether patients with diabetes mellitus show similar alterations. Therefore, we have investigated endothelial function in subcutaneous arteries of normotensive subjects (NT), of patients with essential hypertension (EH), of patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as of patients with both essential hypertension and non-insulin-dependent diabetes mellitus (NIDDM+EH). PATIENTS AND METHODS: All subjects were submitted to a biopsy of the subcutaneous fat Small arteries were dissected and mounted on a micromyograph. The media to lumen ratio (M/L) was calculated. A concentration-response curve to acetylcholine, to bradykinin as well as to the endothelium-independent vasodilator sodium nitroprusside were performed. We also evaluated the contractile response to endothelin-1. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) plasma levels were also measured. RESULTS: The vasodilatation to acetylcholine and bradykinin (but not to sodium nitroprusside) was significantly and similarly reduced in EH, in NIDDM, and in NIDDM+EH compared with NT. The contractile response to endothelin-1 was similarly reduced in EH, in NIDDM and in NIDDM+EH. Plasma ICAM-1 and VCAM-1 concentrations were higher in EH, NIDDM and NIDDM+EH than in NT. CONCLUSIONS: An evident endothelial dysfunction was detected in patients with NIDDM, and the simultaneous presence of EH did not seem to exert an additive effect. The contractile responses to endothelin-1 were reduced possibly as a consequence of ET(A) receptor down-regulation.

Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II Diabetic patients.

A suppressed growth hormone (GH) response to GH-releasing hormone (GHRH) in both lean and overweight type II diabetics has been reported. Pyridostigmine (PD), an acetylcholinesterase inhibitor, elicits GH secretion when administered alone and enhances the GH response to GHRH in normal subjects. The aim of our study was to evaluate the effect of PD on GHRH-stimulated GH secretion in both lean and obese type II diabetic patients. We studied 16 patients with type II diabetes mellitus (seven lean and nine obese). Eleven nondiabetic subjects (six lean and five obese) served as controls. Each subjects underwent treatment with (1) 120 mg PD orally or (2) 2 tablets of placebo orally, 60 minutes before intravenous (IV) injection of 100 micrograms GHRH-(1-29)NH2. We have found no significant differences in GH responses to GHRH between obese diabetics and obese controls. On the other hand, the absolute GH levels were significantly suppressed in lean type II diabetics compared with lean controls at 15 and 30 minutes after GHRH injection. Obese diabetic subjects had slightly but not significantly decreased GH responses to GHRH+PD compared with obese nondiabetic subjects (8.36 +/- 1.62 v 14.4 +/- 7.62 micrograms/L). Lean type II diabetics showed a blunted GH release after GHRH+PD compared with normal-weight healthy subjects (GH peaks, 15.77 +/- 2.17 v 40.88 +/- 6.17 micrograms/L, P < .05). PD enhanced significantly the GH response to GHRH in obese diabetics, obese controls, and non-obese controls (P < .05), but not in non-obese type II diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating adhesion molecules and carotid artery structural changes in patients with noninsulin-dependent diabetes mellitus.

Hypertension and non insulin-dependent diabetes mellitus (NIDDM) are well-known risk factors for atherosclerotic disease. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may exert a relevant role in the pathogenesis of atherosclerosis; their prognostic relevance has been recently demonstrated. The aim of the study was to investigate possible inter-relation between circulating adhesion molecule levels, carotid artery structure and endothelial function in 15 patients with NIDDM, as well as in 15 patients with both NIDDM and essential hypertension (NIDDM+EH) compared with 15 normal subjects (NS) and 15 euglycaemic patients with EH, matched for age, sex and body weight. All subjects were submitted to a biopsy of the gluteal subcutaneous fat. Small arteries were dissected and mounted on a micromyograph, and the media-to-lumen (M/L) ratio was then calculated. Carotid artery structure was investigated by Doppler ultrasound. Endothelial function was evaluated by investigation of the flow-mediated dilatation (FMD) of the brachial artery. ICAM-1 and VCAM-1 plasma levels were measured by ELISA. ICAM-1 and VCAM-1 plasma levels were significantly greater and FMD smaller in EH, NIDDM and NIDDM+EH than in NS, but no difference was observed among the three pathological groups. Carotid artery structural changes were more pronounced in NIDDM+EH. No significant difference was observed among NIDDM, EH and NS. The M/L ratio of subcutaneous small resistance arteries was significantly greater in NIDDM+EH than in NIDDM or EH. NS had a smaller M/L ratio than the other groups. Significant correlations were observed between ICAM-1 plasma levels and indices of carotid artery structure in diabetic patients. However, the relations were close only in NIDDM+EH. In conclusion, our data suggest that NIDDM+EH may present more pronounced vascular structural alterations than NIDDM, and that adhesion molecules plasma levels are closely inter-related with carotid artery structural alterations, at least in NIDDM+EH, but not with M/L ratio of small resistance arteries.

Low-dose octreotide is able to cause a maximal inhibition of the glycemic responses to a mixed meal in obese type 2 diabetic patients treated with insulin.

Short-term studies have shown that octreotide, a long-acting somatostatin analog, blunts postprandial glycemic responses and reduces insulin requirement in insulin treated diabetic patients. The aim of our study was to investigate the effects of three single, different doses of octreotide on the glycemic response to a mixed meal in eight insulin treated type 2 diabetic patients after secondary failure with hypoglycemic agents. Previous treatments were substituted by regular insulin, 0.5 U/kg/day divided into three sc injections, for at least seven days. All patients received: (a) regular insulin (0.1 U/kg, sc) at 7.30 am; (b) octreotide 25 micrograms sc or (c) 50 micrograms sc or (d) 100 micrograms sc simultaneously with insulin but injected at different sites. From 8.00 to 8.15 the patients consumed a preconstituted fluid mixed meal of 250 ml. Following insulin alone a significant increase in blood glucose levels was observed after the meal. Abolished and not significantly different blood glucose responses to the meal after each of the three doses of octreotide were observed. Our findings suggest that with a low dose of octreotide (25 micrograms) it is possible to abolish the postprandial glycemic peak in type 2 diabetic patients treated with insulin.

Reversible myocardial impairment in the Churg-Strauss syndrome: report of a case.

Heart disease is a major cause of morbidity and mortality in the Churg-Strauss syndrome. However, few clinical follow-ups have been published. In this case report, in which the diagnosis of Churg-Strauss syndrome was made based on histologic criteria and clinical features, heart failure with globally depressed left ventricular function was present. Aggressive therapy (prednisone and cyclophosphamide) was instituted. In the follow-up a prompt clinical response and eventual recovery of the indices of cardiac function as evaluated by echocardiography and radionuclide ventriculography were observed.

Short term effect of captopril on microalbuminuria induced by exercise in normotensive diabetics.

OBJECTIVE: To investigate whether captopril has any effect on microalbuminuria induced by exercise in normotensive diabetic patients with early stage nephropathy. DESIGN: Randomised, double blind, crossover trial. SETTING: Outpatient department. PATIENTS: 22 diabetics with stage II nephropathy (urinary albumin excretion rate less than 20 micrograms/min; 15 with type I diabetes and seven with type II), 32 patients with stage III nephropathy (urinary albumin excretion rate 20-200 micrograms/min; 14 with type I diabetes and 18 with type II), and 10 normal subjects. INTERVENTIONS: Four exercise tests on a cycle ergometer: the first two under basal conditions and the third and fourth after subjects had received captopril (two 25 mg doses in 24 hours) or placebo (two tablets in 24 hours). END POINT: Exercised until 90% of maximum heart rate achieved. MEASUREMENTS AND MAIN RESULTS: Mean urinary excretion one hour after the first two exercise tests was 21 micrograms/min in normal subjects, 101 micrograms/min in diabetic patients with stage II nephropathy, and 333 micrograms/min in those with stage III nephropathy. Similar results were obtained after placebo. After captopril the urinary excretion rate one hour after exercise was significantly decreased in diabetics with stage II (36 micrograms/min) and stage III (107 micrograms/min) disease compared with placebo but not in normal subjects. Systolic and diastolic pressures were similar in the three groups after placebo and captopril had been given. CONCLUSIONS: Captopril significantly reduces microalbuminuria induced by exercise in normotensive diabetics without affecting systemic blood pressure. Captopril may reduce renal intracapillary pressure.

Continuous subcutaneous insulin infusion (CSII) in the management of diabetic lipodystrophy: a case report.

A case of diabetic lipodystrophy which showed an improvement after continuous subcutaneous insulin infusion into lipodystrophic areas is reported. The authors feel that this therapeutic regimen could be useful when conventional treatments (the injection of regular purified insulin or dexamethasone-insulin mixtures in the area of the lesion) have failed to obtain good results.

Variability in the growth hormone response to growth hormone-releasing hormone alone or combined with pyridostigmine in type 1 diabetic patients.

In man the GH response to GHRH is variable within and between subjects. Pyridostigmine (PD), an acetylcholinesterase inhibitor, has been shown to reduce the variability of the GH response to GHRH in normal subjects. The aim of this study was to assess the existence of either inter- or intraindividual variability in the GH response to GHRH in type 1 diabetic patients. Moreover, we investigated the effect of PD on such variability in the same patients. Seven (4 females-3 males) nonobese type 1 diabetic patients underwent two experiments performed in consecutive days according to a single-blind protocol: 1) 120 mg oral PD 60 min before iv injection of human (h) GHRH-(1-29) NH2, 100 micrograms in 2 ml of sterile water; 2) oral placebo 60 min before iv injection of 100 micrograms hGHRH. The two experiments were then repeated, following the same procedure, one and two weeks after the start of the study. The GH peaks after GHRH were variable within different subjects but also in the same subject on different occasions. However, the mean GH peak levels after GHRH in the three tests were not significantly different (14.2 +/- 3.5, 15.3 +/- 3, 16.5 +/- 6.4 micrograms/L, respectively), the coefficient of variation for each test was 65%, 51.8%, 102.4%, respectively (mean 73.1 +/- 15.1%). The GH response to GHRH was always significantly enhanced by PD administration: the mean GH peak levels in the three tests were 31.9 +/- 7.1, 44.8 +/- 10.4, 49.9 +/- 13.1 micrograms/L, respectively, without significant differences between tests.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevalence and clinical meaning of insulin-specific IgE antibodies]. / Prevalenza e significato clinico degli anticorpi IgE specifici verso l'insulina.

Systemic and local reactions to insulins in patients affected by insulin-dependent diabetes are uncommon but may be life threatening. Both systemic and local adverse reactions to therapy may be managed by different therapeutic schemes. The availability of human (DNA recombinant) insulin raised hopes that this be the choice treatment for allergic complications. However, controlled studies showed that reaginic (IgE) antibodies are directed to common insulin determinants and not to heterologus protein contaminants. Therefore we investigated in 62 patients undergoing insulin therapy, prevalence and clinical significance of the detection of specific IgE to insulin. Furthermore, we searched for a relationship between atopic status and the presence of antiinsulin IgE. In our study prevalence of specific IgE to insulin was 16.1%. We showed a correlation between clinical symptoms and the presence of specific IgE to insulin, when these antibodies are of an elevated class (R.A.S.T. class 2 or more). When specific IgE were present we detected antibodies to all insulines (bovine, porcine and human) thus confirming that specific IgE are directed to a common antigenic determinant. Finally, we couldn't find a relationship between atopic status and the presence of reaginic antibodies to insulin.

Growth hormone response to thyrotropin releasing hormone and placebo in a group of insulin dependent diabetic patients.

In order to evaluate if the assessment of the paradoxical GH responses to TRH in diabetic subjects could be altered by the presence of spontaneous fluctuations in plasma GH levels, we compared GH responses to TRH and to saline injection in 19 insulin-dependent diabetic patients. We observed significant increments (greater than 5 ng/ml) in plasma GH levels after TRH iv administration in 5 of 19 patients (26%); on the other hand, a significant increase was also observed in 6 patients (31%) after saline. We conclude that, at least in some diabetics, spontaneous GH pulses might be misinterpreted as paradoxical GH responses after a nonspecific stimulus administration. Moreover, the real existence of the paradoxical GH response to TRH has to be assessed using the following strict criteria: a sufficient magnitude in GH increment (greater than 5 ng/ml), the comparison of the kinetics of GH secretion after TRH and saline in the same patient, the presence of a significant GH rise above basal levels within the first 30 min after TRH injection.