Does autoimmune hypothyroidism increase the risk of neurovascular complications in type 1 diabetes?

BACKGROUND: Type 1 diabetes (T1DM) often coexists with other autoimmune diseases, most commonly with hypothyroidism. To date, the influence of coexisting autoimmune hypothyroidism (AHT) on the course of chronic neurovascular complications of autoimmune diabetes has not been established. The aim of the study was to assess the relationship between AHT and the occurrence of chronic T1DM complications. METHODS: The study group comprised 332 European Caucasian participants with T1DM [165 (49.7%) men]. AHT was recognized in subclinical and overt hypothyroidism and confirmed by the presence of anti-thyroid autoantibodies: anti-peroxidase (ATPO) and/or anti-thyroglobulin (ATg) and ultrasonography (hypoechogenicity, parenchymal heterogeneity, lymph nodes assessment). RESULTS: In the analyzed group, 48.5% of patients were diagnosed with at least one neurovascular complication. At the time of enrollment, 16.3% of participants were diagnosed with AHT. Patients with AHT, compared to those without AHT, were characterized by a higher prevalence of neurovascular complications (64.8 vs. 45.3%; P = 0.009) and retinopathy (55.6 vs. 38.9%; P = 0.02). There were significant differences between groups with and without neurovascular complications, with regard to classic risk factors for chronic diabetes complications: age, T1DM duration, SBP, DBP, HbA1c, TG, eGFR and hypertension prevalence. In the multivariate logistic regression analysis, AHT was an independent predictor of neurovascular complications after adjusting for age, DBP, HbA1c and TG (odds ratio, 2.40; 95% confidence interval, 1.17-4.92; P = 0.02). CONCLUSIONS: AHT coexisting with T1DM was associated with a higher incidence of neurovascular complications.

Accumulation of advanced glycation end products in the skin is accelerated in relation to insulin resistance in people with Type 1 diabetes mellitus.

AIM: To evaluate the association between skin advanced glycation end products and insulin resistance in Type 1 diabetes. METHODS: The study group consisted of 476 people with Type 1 diabetes (247 men) with a median (interquartile range) age of 42 (33-53) years, disease duration of 24 (19-32) years and HbA1c concentration of 63 (55-74) mmol/mol [7.9 (7.2-8.9)%]. Insulin resistance was assessed according to estimated glucose disposal rate. Advanced glycation product accumulation in the skin was measured by autofluorescence using an AGE Reader. The group was divided into three subgroups based on estimated glucose disposal rate tertiles (<5.5, 5.5-9.5 and >9.5 mg/kg/min, respectively). The higher the estimated glucose disposal rate, the lower the insulin resistance. RESULTS: Skin autofluoresence level decreased with increasing estimated glucose disposal rate; comparing people below the lower tertile, with those between the first and third tertiles, and with those above the third tertile, the median autofluoresences were, respectively: 2.5 (2.2-2.9) vs 2.3 (2.0-2.7) vs 2.1 (1.9-2.5) AU (P<0.0001). A negative correlation was observed between skin autofluorescence and estimated glucose disposal rate (Spearman's correlation coefficient=-0.31, P <0.001). Multiple logistic regression showed a significant, two-way association of insulin resistance with skin autofluorescence. CONCLUSION: The results of this study offer strong evidence for a two-way relationship between insulin resistance and advanced glycation product accumulation in the skin in people with Type 1 diabetes.

The relationship between sudomotor function and skin microvascular reactivity in individuals with type 1 diabetes of long duration.

AIM: The aim of this study was to assess the relationship between sudomotor function and microvascular perfusion in patients with type 1 diabetes (DM1). METHODS: We evaluated 415 patients (206 women), with DM1, median age of 41 (IQR: 33-53) years, disease duration of 25 (IQR: 20-32) years. We assessed metabolic control of diabetes and the presence of peripheral and cardiac autonomic neuropathy. Sudomotor function was assessed using Sudoscan device by electrochemical skin conductance (ESC). Microvascular function was measured by laser-Doppler flowmetry with basal perfusion, the peak flow after occlusion (PORHpeak) and THmax which is the percentage change between basal perfusion and the peak flow during thermal hyperemia (TH). The accumulation of advanced glycation end products in the skin was assessed by skin autofluorescence (AF) measurement using AGE Reader. We subdivided patients based on the presence of diabetic peripheral neuropathy (DPN), cardiac autonomic neuropathy (CAN) and according to normal value of ESC. RESULTS: Patients with abnormal ESC had higher skin AF [2.5 (2.1-2.9) vs 2.1 (1.9-2.5) AU, p < 0.001], lower eGFR [83 (72-96) vs 98 (86-108) ml/min/1.73 m2, p < 0.001], higher basal perfusion [25 (12-81) vs 14 (7-43) PU, p < 0.001], lower THmax [664 (137-1461) vs 1115 (346-1933) %, p = 0.002], higher PORHpeak [104 (59-167) vs 70 (48-135) PU, p < 0.001] as compared to subjects with normal ESC results. We found negative correlation between THmax and TG level (Rs = -0.14, p < 0.005), AF (Rs = -0.19, p = 0.001), vibration perception threshold - VPT (Rs = -0.24, p < 0.001) and positive correlation with HDL level (Rs = 0.14, p = 0.005), Feet ESC (Rs = 0.21, p < 0.001) and Hands ESC (Rs = 0.14, p = 0.004). We found positive correlation between PORHpeak and TG level (Rs = 0.14, p = 0.003), skin AF (Rs = 0.29, p < 0.001), VPT (0.27, p < 0.001) and negative correlation with eGFR (Rs = -0.2, p < 0.001), HDL (Rs = -0.12, p = 0.01), Feet ESC (Rs = -0.27, p < 0.001) and Hand ESC (Rs = -0.16, p = 0.002). CONCLUSION: Impaired microvascular reactivity is associated with sudomotor dysfunction in patients with type 1 diabetes.

Left atrial appendage closure - new choice for no-option patients with atrial fibrillation.

AIM: Remodeling and impaired blood flow in left atrial appendage (LAA), which occurs in patients with atrial fibrillation (AF), may lead to thrombus formation and possible thromboembolic complications. Although there are several pharmacological antithrombotic possibilities, some patients with several co-morbidities and contraindications to such treatment cannot be offered any of them. Therefore LAA closure systems may be an attractive alternative. We present our early experience with two currently available different LAA transcatheter closure systems (Watchman and Amplatzer Cardiac Plug). METHODS: Twenty three patients (mean age 69.1±6.8 years, 12 male) with non-rheumatic AF and high risk of thromboembolic complications (CHA2DS2-VASc score ≥2 (mean 4.5±1.5), who could not be treated with the long-term oral anticoagulation because of contraindications or significant side effects, were qualified to the LAA closure. RESULTS: The Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN, USA) was implanted in 7 patients and Watchman Occluder (Boston Scientific, Boston, MA, USA) in the other 15 patients. The implantation was not performed in one patient as the transoesophageal echocardiography during the procedure revealed a new thrombus in LAA. The procedural details and follow-up data are presented. Neither severe pericardial effusion nor device related thrombus were observed. In long term follow-up transient ischemic attack was noted only in one patient (diagnosed with thrombophilia). One patient died 14 months after the procedure due to non-cardiac reason. CONCLUSION: The LAA occluder implantation seems to be a safe and reasonable alternative for oral anticoagulation and should be considered in patients with AF who have contraindications or complications of pharmacological treatment.

Does serum cystatin C level reflect insulin resistance in patients with type 1 diabetes?

OBJECTIVES: The aim of study was to evaluate the relationship between serum cystatin C and insulin resistance (IR) in type 1 diabetic patients being the participants of Poznan Prospective Study. DESIGN AND METHODS: The study was performed on 71 Caucasian patients (46 men); with type 1 diabetes, who were recruited into the Poznan Prospective Study, at the age of 39±6.1 meanly, and treated with intensive insulin therapy since the onset of the disease. The follow-up period and diabetes duration were 15±1.6 years. Insulin resistance (IR) was assessed by estimated glucose disposal rate (eGDR) calculation with cut-off point 7.5 mg/kg/min. Patients were divided into two groups, according to the presence or absence of IR. RESULTS: From among 71 patients, 31 patients (43.7%) presented decreased sensitive to insulin with eGDR below 7.5 mg/kg/min. Patients who had eGDR <7.5 mg/kg/min (insulin resistant), compared with subjects with eGDR >7.5 mg/kg/min (insulin sensitive), had higher level of serum cystatin C [0.59 (IQR:0.44-0.84) vs 0.46 (IQR:0.37-0.55) mg/L, p=0.009]. A significant negative correlation between cystatin C and eGDR was revealed (Rs=-0.39, p=0.001). In regression model cystatin C was related to insulin resistance, adjusted for sex, BMI, eGFR and duration of diabetes [OR 0.03 (0.001-0.56), p=0.01]. CONCLUSIONS: Higher level of serum cystatin C is related to decreased insulin sensitivity in patients with type 1 diabetes. This relationship seems to have an important clinical implication.

Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy.

BACKGROUND: Various skin diseases are commonly observed in diabetic patients. Typical biophysical properties of diabetic skin such as lower skin elasticity, decreased water content in stratum corneum, increased itching and sweating disturbances are reported. The aim of the study was to examine the distribution and intensity of skin pigmentation in diabetic patients in correlation with the metabolic control and with presence of microangiopathy. MATERIAL AND METHODS: The study was conducted on 105 patients (42 men and 63 women, median age 31), with type 1 diabetes (DM1). The control group of 53 healthy individuals (22 men and 31 women) was age- and sex-matched. Skin pigmentation was measured at 3 different locations of the body (cheek, dorsal surface of a forearm and dorsal surface of a foot) using Mexameter® MX 18. We calculated melanin index (MI) by the meter from the intensities of absorbed and reflected light at 880 nm. RESULTS: Patients with DM1 had lower MI on the foot (173.2 ± 38.8 vs. 193.4 ± 52.7, p=0.016) as compared to controls. In the univariate analysis cheek MI was negatively related to HbA1c level (ß=-4.53, p=0.01). Forearm MI was negatively associated with daily insulin dose (ß=-0.58, p=0.01), BMI (ß=-3.02, p<0.001), waist circumference (ß=-0.75, p=0.009), serum TG concentration (ß=-18.47, p<0.001) and positively with HDL cholesterol level (ß=15.76, p=0.02). Diabetic patients with hypertension had lower foot MI values (ß=-18.28, p=0.03). Lower MI was associated with the presence of diabetic neuropathy (ß=-18.67, p=0.04) and retinopathy (ß=-17.47, p=0.03). CONCLUSIONS: In conclusion, there seems to be loss of melanocytes in type 1 diabetes. The melanin content is related to glycemic control of diabetes and obesity. The lower melanin content the higher possibility of microangiopathy. This is a first report in the literature devoted to distribution of melanin in the skin of type 1 diabetic patients.

Higher risk of microvascular complications in smokers with type 1 diabetes despite intensive insulin therapy.

AIM: The aim of the study was to evaluate the relationship between smoking status and the incidence of microvascular complications in patients with type 1 diabetes (DM1), treated with intensive functional insulin therapy (IFIT) from the onset of the disease. METHODS: 81 participants (51 men, 30 women) of Poznan Prospective Study (PoProStu) with mean age of 34.0 ± 6.4 years were included in this analysis. Patients were observed for 10.0 ± 1.5 years. Evaluation of microvascular complications of diabetes, such as retinopathy, diabetic kidney disease and neuropathy was performed. Patients were divided into two groups depending on the smoking status: smokers and non-smokers. RESULTS: In the group of smokers (n=36) in comparison with patients who had never smoked (n=45) any microangiopathy (58.3% vs 33.3%, p=0.02), retinopathy (44.4% vs 20%, p=0.02), diabetic kidney disease (47.2% vs 24.4%, p=0.03) and neuropathy (25% vs 4.4%, p=0.02) were found more often. A significant relationship, adjusted for age, sex, duration of diabetes, presence of hypertension and HbA1c between smoking and neuropathy and retinopathy was revealed [OR 10.16 (95%CI 1.59-64.95); p=0.01 and OR 3.50 (95%CI 1.01-12.12); p=0.04, respectively]. CONCLUSION: The results show that in patients with DM1, there is a strong relationship between smoking and the diabetic microvascular complications, especially with neuropathy, despite treatment from the initial diagnosis with intensive insulin therapy.

Carotid intima-media thickness and arterial stiffness in type 1 diabetic patients are dependent on age and mean blood pressure.

AIM: The aim of the study was to assess the factors that influence carotid intima-media thickness (CIMT) and arterial stiffness in type 1 diabetic patients. MATERIAL AND METHODS: We included 87 type 1 diabetic patients (44 women, 43 men), median age 34 years, disease duration 10 years, HbA1c 8.2%. CIMT was measured using high resolution ultrasonography. Arterial stiffness was assessed with the use of digital volume pulse analysis and tonometric measurement of wave reflection and central haemodynamics. Serum C-reactive protein (hsCRP), matrix metalloproteinase-9 (MMP-9), soluble intracellular adhesion molecule-1 (sICAM-1) and myeloperoxidase (MPO) concentrations were also measured. RESULTS: CIMT and arterial stiffness correlated with age, duration of diabetes, systolic and diastolic blood pressure, GFR-glomerular filtration rate and sICAM-1. Multiple regression analysis identified only age as significant determinant of CIMT. Age, mean blood pressure and GFR, but not duration of diabetes were significant determinants of arterial stiffness. CONCLUSIONS: In type 1 diabetic patients both CIMT and arterial stiffness were related to age, blood pressure, kidney function and sICAM-1 serum concentration.

Insulin resistance is associated with microangiopathy in type 1 diabetic patients treated with intensive insulin therapy from the onset of disease.

AIM: The aim of the study was to evaluate the relationship between indirect parameters of insulin resistance (IR) and risk of microangiopathy in patients with type 1 diabetes (DM1), treated from the initial diagnosis with intensive insulin therapy. METHODS: The study group consisted of 81 patients with DM1 (51 men, 30 women), aged 34±6.4, and who were observed for 10±1.5 years. Indirect parameters of IR were evaluated: waist circumference, waist to hip ratio (WHR), body mass index (BMI), daily insulin requirement, gain of weight from the beginning of the disease, lipid profile, estimated glucose disposal rate (eGDR), inflammatory markers and features of metabolic syndrome. Patients were divided into two groups depending on the presence or absence of microangiopathy. RESULTS: In the group with microangiopathy (n=36) in comparison with patients without complications (n=45) we found: larger waist circumference (88.9±11.7 vs. 83.7±10.2 cm; p=0.036), higher weight before diabetes (77.3±17.0 vs. 67.0±12.5 kg; p=0.008), higher WHR (0.90±0.08 vs. 0.86±0.08; p=0.048), higher level of triglycerides (1.3±0.8 vs. 0.9±0.3 mmol/l; p=0.002) and lower eGDR (7.2±2.4 vs. 8.8±1.9 mg/kg/min; p=0.0019). In patients with microangiopathy, features of metabolic syndrome were found more often (12 (33.3%) vs. 4 (8.9%); p=0.006). A significant relationship, adjusted for sex, age and duration of diabetes, between eGDR and microangiopathy was revealed (OR 0.65 (95%CI 0.49-0.86); p=0.0037). CONCLUSION: The results show that in patients with DM1, treated from the initial diagnosis with intensive insulin therapy, there is an independent relationship between IR and the diabetic microangiopathy.

Generic olanzapine: health authority opportunity or nightmare?

Pressures to contain pharmaceutical expenditure have led to increased prescribing and dispensing of generic drugs in addition to low prices for generics. Atypical antipsychotics are prescribed for schizophrenia leading to resource pressures with their higher acquisition costs than typical antipsychotics. Drug costs can be reduced once multiple sources are available. However, this must be balanced against possible efficacy, safety and compliance concerns given the high cost of relapses for patients with schizophrenia. Generic clozapine has been launched. There was an increase in relapse rates with early formulations in the USA. However, this has not been the case with more recent formulations. Despite this, there could be patient and physician concerns when additional generic atypicals, such as olanzapine are available, reducing potential savings. A retrospective survey of patients prescribed Zyprexa((R)), generic olanzapine or both, over an extensive period was undertaken in Poland to help address these concerns given the difficulties with conducting randomized clinical trials with generics in complex situations. The survey showed similar effective doses of olanzapine in all groups. Relapse rates were similar in patients before and after switching to generic olanzapine, and no untoward side effects were seen in any patient prescribed generic olanzapine. Consequently, generic olanzapine should be welcomed with savings redirected to improving compliance or funding new premium priced drugs that can reduce relapses in refractory patients. This should give reassurance to health authorities to continue their reforms where pertinent to optimize resources by increasing availability of generics.

Assessment and prevalence of depression in women 45-55 years of age visiting gynecological clinics in Poland: screening for depression among midlife gynecologic patients.

The aims of the Polish survey were to assess efficacy of screening for depression in gynecological practice and to estimate prevalence of depressive disorders in midlife women visiting gynecologists. The study included 2262 female outpatients aged 45-55, who were screened by 120 gynecologists throughout Poland. Patients completed the Beck's Depression Inventory (BDI) and were assessed by gynecologists to verify the presence of symptoms of a current Depressive Episode according to ICD-10 diagnostic criteria. Patients who obtained a score of 12 points or more on the BDI were referred for psychiatric evaluation, including the modified version of Mini International Neuropsychiatric Interview (MINI). The study showed that gynecologists in Poland are able to perform screenings for depression effectively in outpatient settings. Results also suggested that about 19% of women aged 45 to 55 years visiting gynecologists may suffer from depressive disorders.

Dexamethasone suppression test and suicide attempts in schizophrenic patients.

The suicide attempts were assessed in 32 schizophrenic patients on whom the dexamethasone suppression test (DST) was done twice in the course of illness: in the years 1985-91 and 1996-97. In the 1985-91 period, both baseline and post-dexamethasone cortisol levels were significantly higher in the patients with previous suicide attempts and baseline cortisol was higher in the patients who were to make a future attempt. In 1996-97, DST non-suppression was shown in more than half of the patients with a history of suicide attempt and in none of those without such history: all cortisol levels were significantly higher in the patients with a history of suicide attempt. Although the mean intensity of depression was higher in the patients with a history of suicide attempt, no association between the intensity of depression and present or previous DST non-suppression status was found. It is suggested that the hyperactivity of the hypothalamic-pituitary-adrenal axis may constitute an element of diathesis for suicidal behavior in schizophrenic patients.

[The case of central pontine myelinolysis in an alcohol dependent male]. / Przypadek mielinozy srodkowej mostu u mezczyzny uzaleznionego od alkoholu.

Long-term alcohol abuse can lead to numerous central nervous system lesions, among them central pontine myelinolysis. In this paper, the first in Polish literature case of central pontine myelinolysis in an alcohol dependent male, clinically diagnosed, and confirmed by nuclear magnetic resonance with one year follow-up has been presented. The patient, 49 years old, was admitted to Addiction Treatment Unit, Department of Psychiatry in Bydgoszcz. After admission he manifested clouded consciousness, dysphasia, hyponatremia and neuropsychological abnormalities which showed brain stem lesion. He had no significant abnormalities in CT. Nuclear magnetic resonance revealed triangular hypointensive lesion 10 x 5 mm in central pontine region. One year after admission to Addiction Treatment Unit he still has troubles with walking and swallowing. He has bilateral pyramidal symptoms and emotional lability. He was treated with vinpocetine (0.075 g per day), piracetam (4.8 g per day) and chlorprotixen (0.09 g per day). He was admitted to Psychiatric Ward because of a suicidal attempt as a manifestation of mood disorder due to general medical condition.

Hoigne's syndrome, kindling, and panic disorder.

A review of Hoigne's syndrome (HS) is presented, and 47 cases of putative procaine penicillin-induced HS are discussed within the context of kindling models of human psychopathology. Sixty percent of the individuals with HS in our retrospective study reported a lifetime history of panic disorder. The risk factors and causal relationships among repeated injection of procaine penicillin, HS, and anxiety disorders, particularly panic disorder, require further investigation.

[Group psychotherapy of neuroses and personality disorders in regular soldiers]. / Psychoterapia grupowa nerwic i zaburzen osobowosci u zolnierzy zawodowych.

Environmental conditions cause neuroses and symptoms of personality disorders in regular soldiers. Military service in highly formalized and hierarchical conditions makes it impossible to: express emotions (particularly negative ones), to arrange one's own time, to choose the position and place of work. Another important psychotraumatic factor is excessive load of work and responsibility for the sake of "the service". Psychotherapy is the main part of neurotic and personality disorder therapy in regular soldiers. The social context is the bass for theoretical assumptions of psychotherapy carried out by the authors. Based on the theory of learning, the aims of the applied psychotherapy are: eagerness for the elimination of symptoms and changing the mode of behaviour. Group psychotherapy is carried out in stationary conditions, in groups of 8 to 13 patients, for 8-9 weeks. The applied methods are: debating psychotherapy, interaction-communicative methods, psychodrawing, musicotherapy, choreotherapy and relaxation techniques. As the result of the therapy, about 89% of symptomatic improvement and about 81% of the change of attitude and behaviour were obtained.

[Procaine kindling in acute non-allergic reaction to procaine penicillin G]. / Kindling prokainowy w ostrej niealergicznej reakcji na penicyline prokainowa.

On the basis of the analysis of acute nonallergic reaction to a course of procaine penicillin G, the authors have stated that symptoms of this reaction result from the irritation of temporal limbic structures. The authors think that it is connected with procaine kindling mechanism, the procaine component of the drug.

[Diagnosis and treatment of injuries of the brachial plexus in our experience]. / Wlasne doswiadczenia w diagnostyce i leczeniu urazów splotu ramiennego.

The subject of the paper is an analysis of the pathomechanism of injuries and results of multispecialist diagnostic investigations and surgical treatment in 74 cases of traumatic brachial plexus injuries observed in a period of 5 years. The observations of the authors suggest the following conclusions: Direct injury to the brachial plexus requires emergency or delayed emergency surgical intervention. In indirect and secondary traumatic injuries of the plexus the best results are obtained by possibly early reconstructive operation carried out after establishing indications to surgical treatment. The optimal time for full diagnosis of brachial plexus injury and its surgical treatment is between 3 and 6 months after trauma. The full diagnosis of brachial plexus injury should include: radiological examination of the cervical spine with radiograms in flexion and extension (if necessary) and contrast investigations (myelography) of the vertebral canal for determining canal patency and cerebrospinal fluid changes and dynamics. Electromyography is one of the principal elements of the diagnostic procedures used for the localization of plexus damage and for evaluation of the return of function after surgery. It would be indicated to organize in Poland special hospital departments or centres for systematic diagnostic investigations and surgical treatment of patients with brachial plexus injury.