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Aims: The effects of continuous subcutaneous insulin infusion (CSII) therapy with or without continuous glucose monitoring (CGM) on neonatal outcomes and glycemic outcomes of pregnant women with type 1 diabetes (T1D), living in Poland, were assessed., Methods: This prospective observational study enrolled women with T1D (N = 481, aged 18-45 years) who were pregnant or planned pregnancy. All used CSII therapy and a subset used CGM with CSII (CSII + CGM). Neonatal outcomes (e.g., rate of large for gestational age [LGA] delivery [birth weight > 90th percentile]) and maternal glycemia (e.g., HbA1c and percentage of time at sensor glucose ranges) were evaluated., Results: Overall HbA1c at trimesters 1, 2, and 3 was 6.8 ± 1.1% (50.9 ± 12.3 mmol/mol, N = 354), 5.8 ± 0.7% (40.1 ± 8.0 mmol/mol, N = 318), and 5.9 ± 0.7% (41.4 ± 8.0 mmol/mol, N = 255), respectively. A HbA1c target of < 6.0% (42 mmol/mol) at each trimester was achieved by 20.9% (74/354), 65.1% (207/318), and 58.0% (148/255), respectively. For women using CSII + CGM versus CSII only, HbA1c levels at trimesters 1, 2, and 3 were 6.5 ± 0.9% versus 7.1 ± 1.3% (47.8 ± 9.7 mmol/mol versus 54.3 ± 14.0 mmol/mol, p < 0.0001), 5.7 ± 0.6% versus 6.0 ± 0.9% (38.9 ± 6.5 mmol/mol versus 41.6 ± 9.3 mmol/mol, p = 0.0122), and 5.8 ± 0.6% versus 6.1 ± 0.8% (40.3 ± 6.9 mmol/mol versus 42.9 ± 9.1 mmol/mol, p = 0.0117), respectively. For the overall, CSII only, and CSII + CGM groups, rates of LGA delivery were 22.7% (74/326), 24.6% (34/138), and 21.3% (40/188), respectively., Conclusions: Observational assessment of women with T1D using CSII therapy demonstrated low HbA1c throughout pregnancy and low rates of LGA. The addition of CGM to CSII therapy compared to CSII therapy alone was associated with some improved maternal glycemic and neonatal outcomes., Gov Identifier: NCT01779141 (January 2013)., (© 2023. The Author(s).)

Background: ARETAEUS 1 study showed that a great majority of patients with type 2 diabetes mellitus (T2DM) of short duration did not meet all of the treatment goals. Since then the treatment goals in T2DM have been changed. The aim of the ARETAEUS 2-Grupa Study was to assess cardiovascular (CV) risk management and meeting treatment goals in the population of T2DM of more than 10-year duration., Methods: ARETAEUS2-Grupa was a cross-sectional questionnaire-based study conducted in Poland in 2012. Randomly selected physicians recruited 1,740 patients with T2DM diagnosed more than 10 years before the study., Results: Lipid treatment goals were met respectively: for total cholesterol in 34.5% of all patients, triglycerides in 53.8%, low density lipoprotein cholesterol (LDL-C) in 26.5% and high density lipoprotein cholesterol (HDL-C) in 38.2%. Most of patients with and without coronary artery disease were receiving aspirin (90.3% and 60%, respectively) and statins (84.4% and 67.7%, respectively). The current blood pressure (BP) goal (140/90 mm Hg) was met in 43.5% of patients and the previous goal (< 130/80 mm Hg) in 12.4%. The patients were mainly treated with ≥ 3 antihypertensive drugs. All treatment goals (for HbA1c, BP and LDL-C) were reached only by 8.2% of patients, any two goals by 26.3% of patients, one goal by 39.8% of patients, none by 25.6% of patients., Conclusions: The new less restrictive treatment goals are reached more frequently but still much is to be done in the field of clinical practice guidelines implementation and CV prevention in T2DM population.

Introduction: Previous studies have shown insufficient diabetes control in patients with type 2 diabetes (T2DM). Diabetes Poland changed the target HbA1c and blood pressure (BP) values in diabetic patients in their practice guidelines in 2011, that were further sustained. To assess the management and treatment choices in T2DM of more than ten years' duration and the degree to which diabetic control criteria recommended by the Diabetes Poland clinical practice guidelines 2012 are being met., Material and Methods: ARETAEUS2-Grupa was a cross-sectional questionnaire-based study conducted in Poland in 2012 (April-June). It involved 1,740 patients of any age and both genders, with T2DM diagnosed more than ten years before the study, and recruited by randomly selected physicians., Results: All patients received pharmacological treatment, most of them combination therapy or insulin in monotherapy. 40% of patients met the goal for HbA1c control (≤ 7%) and the median value of HbA1c was above the recommended threshold (7.2%). Only 8% of thetotal population met all three goals (HbA1c, BP and lipid levels), 26% - two goals, and 40% - only one goal. Over 25% of patients did not meet any of the treatment goals., Conclusions: We observed considerable deviations from treatment targets recommended by current clinical practice guidelines for patients with T2DM of more than ten years' duration. The frequency of cardiovascular risk factors and late diabetes complications was high, while a relatively high percentage of patients was not examined for late diabetes complications.

Introduction:  In 2011, the Diabetes Poland updated its recommended goals in diabetes treatment, including hemoglobin A1c (HbA1c) and blood pressure (BP) levels. Adherence to the updated guidelines has not been systematically assessed so far., Objectives:  The aim of the study was to assess which methods are most commonly used in the treatment of recently diagnosed type 2 diabetes and to what extent the new criteria for diabetes control are met in these patients., Patients and Methods:  The ARETAEUS2‑Grupa study was a cross‑sectional questionnaire‑based study conducted in Poland in 2012 (April-June). It involved 1636 patients of any age and sex, with type 2 diabetes diagnosed within the previous 2 years, recruited by randomly selected physicians., Results:  Of all patients, 37.5% met the goal of an HbA1c level of ≤6.5% (recommended in type 2 diabetes of short duration), while 62% met the goal of an HbA1c level of ≤7% (general recommendation). Only 6.7% of the patients met all 3 goals (HbA1c ≤6.5%, BP <140/90 mmHg, and low‑density lipoprotein cholesterol <100 mg/dl or <70 mg/dl in coronary heart disease), 29.7% met 2 goals, 36.8% met only 1 goal, while 26.7% did not meet any of the treatment goals. With the use of the HbA1c level recommended for the overall population, the proportions of patients meeting 3, 2, and 1 goals increased to 11%, 34.5%, and 35.5%, respectively, while the percentage of the patients not meeting any goals decreased to 18%. Metformin in monotherapy or in combination was the most commonly used drug in the study population (80%). , Conclusions:  The majority of the patients with type 2 diabetes of short duration did not meet any of the treatment goals as recommended in the current practice guidelines. When the treatment goals were used for the overall population (HbA1c ≤7%), a slightly higher, but still unsatisfactory, proportion of the patients met all the treatment goals. Metformin alone or in combination was the most commonly used drug in the study population.

Introduction: While clinical practice guidelines reflect the best known evidence-based approach to patient care, it is individual clinicians and patients who make decisions and treatment choices, and individual patients who actually achieve (or not) the treatment goals., Objectives: The aim of the study was to describe the population of diabetic patients attending specialty outpatient clinics, to characterize the management of patients with different types of diabetes, and to assess the accordance of management with the recommendations developed by Diabetes Poland., Patients and Methods: The OPTIMO observational study was conducted from 2006 to 2009 and included patients with diabetes diagnosed according to the 1999 World Health Organization criteria who were observed for 1 to 3 years, with control visits at least every 6 months. Participating physicians used pocket PCs equipped with specially developed software to collect patients' data and to provide educational reminders to clinicians., Results: The final analysis involved 9600 patients for whom valid baseline questionnaires were available. Type 2 diabetes was observed in 92% and type 1 diabetes in 6% of the patients. Mean age was 60.5 years. Women constituted 54% of the population. Coronary heart disease was observed in 32% and arterial hypertension in 76% of the patients. At baseline, 23% of the patients had hemoglobin A1c level below 6.5% and 44% below 7.0. Total cholesterol and triglycerides treatment goals were met at baseline by slightly more than half of the patients, while low-density lipoprotein cholesterol treatment goal was met only by 33% of the patients. Baseline blood pressure below 130/80 mmHg was reported for 11% of the patients., Conclusions: At the beginning of the OPTIMO study, we have observed considerable deviations from treatment targets recommended by current clinical practice guidelines for diabetic patients, which leaves significant room for improvement in the care of diabetic patients.

One of the attributes of CSII (continuous subcutaneous insulin infusion) is its ability to tailor prandial insulin delivery to the composition of a meal and anticipated glycemic effects. The dual-wave bolus (DWB) is a tool implemented in contemporary insulin pumps that delivers a combination of an instant insulin bolus followed by a square bolus (SB) infused over several hours. We assessed the effectiveness of DWB in 56 adult patients with type 1 diabetes (T1DM) who were on continuous subcutaneous insulin infusion via insulin pump for at least 2 years. We divided patients into frequent (DWB+, n = 32) and infrequent (DWB-, n = 24) DWB users (>20% vs. <20% of daily bolus dose delivered as SB). CSII implementation resulted in a decrease of adjusted HbA1c level by 0.80% (95% CI 0.67-0.93, P < 0.0001) and adjusted mean glycemia by 18.4 mg/dl (95% CI 15.3-21.4, P < 0.0001) in the whole cohort within the first year of observation. It was sustained in the second year, but without further improvement. Frequent DWB use was associated with male sex (59% vs. 17%, p = 0.001) and shorter duration of T1DM (3.4 vs. 11.3 yrs, p < 0.0001), but not with patients' age (25.7 vs. 27.0 years, P = 0.6). DWB+ patients improved their HbA1c by 0.45% more (95% CI 0.20-0.71, P = 0.0009) than DWB- individuals. In conclusion, DWB might be a tool potentially helping to improve glycemic control in T1DM adult users of insulin pumps. Male patients and those with a shorter duration of diabetes seem to use it more willingly.

Background: The practice guidelines of cardiological and diabetological societies emphasise that cardiovascular (CV) risk control in diabetic patients is especially important and should be stricter than in subjects without diabetes. There are little data on the frequency of meeting treatment goals in patients with newly diagnosed diabetes mellitus type 2 (DM2)., Aim: To characterise Polish patients with DM2 diagnosed within the previous two years and to assess if the treatment targets from the current (2008) guidelines of Diabetes Poland regarding control of CV risk factors are met., Methods: ARETAEUS1 was a cross-sectional questionnaire-based study conducted in various regions of Poland in 2009 (January-April). It involved 1,714 patients of all ages and both genders, who had DM2 treated for less than 24 months. They were recruited by randomly selected physicians., Results: Total cholesterol treatment goal (< 4.5 mmol/L) was met in 22% of all patients, triglycerides treatment goal (< 1.7 mmol/L) in 44%, LDL cholesterol treatment goal (< 2.6 mmol/L) in 20% and HDL cholesterol treatment goal (> 1.0 mmol/L in men and > 1.3 mmol/L in women) in 55%. Only 13% of the overall population met the goal of blood pressure (BP) below 130/80 mm Hg. When a less restrictive BP control threshold (< 140/90 mm Hg) was applied, 48% of patients had their BP below the threshold. In the analysis of subgroups (patients with and without previous CV events; receiving 1-5 or not receiving antihypertensive drugs; receiving and not receiving statins and fibrates) we observed from 0% to 3.3% of patients meeting three (HbA1c, BP and cholesterol) treatment goals. The percentages of patients meeting two out of three treatment goals were between 8% and 33% in different subgroups. The percentages of patients meeting only one out of three treatment goals ranged from 27.8% to 46.7% or at least one - from 39% to 69%., Conclusions: Most patients with newly diagnosed diabetes are not meeting their treatment goals regarding control of CV risk factors, which indicates relatively low adherence to national guideline recommendations for diabetes control and primary CV prevention in DM2. Difficulties in achieving CV treatment targets in the diabetic population indicate the need for a great deal of effort on the part of clinicians and patients. Practice guidelines developers should consider what treatment targets are achievable at a reasonable expense of effort.

Introduction: There is a paucity of data on meeting treatment goals in patients with newly diagnosed type 2 diabetes (DM2)., Objectives: The aim of the study was to characterize Polish patients with newly diagnosed DM2, to assess management of hyperglycemia, and to estimate the proportion of patients achieving the criteria of disease control recommended by the national clinical practice guidelines published in 2008., Patients and Methods: ARETAEUS1 was a cross-sectional questionnaire-based study conducted in several regions of Poland in 2009 (January-April). It involved 1714 patients with DM2 of any age and sex, treated for less than 24 months, and recruited by randomly selected physicians., Results: Only 28.9% of patients with DM2 met the goal for glycated hemoglobin (HbA1c) control (<6.5%). In the total population, only 1.4% of all patients met all 3 goals (HbA1c, blood pressure, and lipid levels), 12.5%--2 goals, and 35.3%--only 1 goal; 50.7% did not meet any of the treatment goals. Achieving all of the treatment goals varied between the patient subgroups (in relation to the current diabetes treatment, age, sex, body mass index, and diabetes duration)., Conclusions: Most patients with newly diagnosed DM2 do not meet all their major treatment goals, which indicates relatively low adherence to the national guideline recommendations for diabetes control and primary cardiovascular prevention in DM2. Metformin seems to be underused and titration of other glucose lowering medications may be insufficiently target-driven. Assuming that adherence to the current clinical practice guidelines is beneficial for patients, we recommend that both practitioners and patients have increased awareness of these guidelines and of the ways to achieve and maintain treatment goals.

Background: Two regimens are used to achieve excellent glycemic control during pregnancy in type 1 diabetes mellitus (T1DM): continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). We assessed their efficacy and safety and the effect of pregnancy planning., Methods: We examined 269 pregnant T1DM women: 157 treated with MDI (MDI group), 42 with CSII (CSII group), and 70 who switched from MDI to CSII in the first trimester (MDI/CSII group). There were 116 women who planned pregnancy: 58 in the MDI group, 38 in the CSII group, and 20 in the MDI/CSII group. The estimated differences in glycemic control and maternal and fetal outcomes were adjusted for baseline characteristics., Results: Mean glycated A1c (HbA1c) in the first trimester in the whole group was 6.9%, and the women differed depending on whether they planned pregnancy or not (P < 0.0001). A multiple regression model showed an average difference of about 0.9% in favor of pregnancy planning, with no interaction between the planning and treatments. In the second trimester, HbA1c decreased to a mean value of 5.8%, with improvement of HbA1c across all treatments: by 1.5% in not-planning and 0.9% in planning women. Despite greater improvement, not-planning women still had a higher HbA1c (by 0.3%, P = 0.05). In the third trimester, there was no further significant changes; nevertheless, women who planned pregnancy still had a lower HbA1c (by 0.5%, P = 0.02). There were 14 malformations, stillbirths, and perinatal infant deaths in the not-planning versus five in the planning group (P = 0.07). Patients in the CSII group had a 2 kg greater weight gain compared to the MDI group (15.0 kg vs. 13.0 kg; P = 0.005)., Conclusions: In pregnancy with T1DM, both MDI and CSII can provide excellent glycemic control. Pregnancy planning has a beneficial effect on glycemic control, independent from the therapy model. CSII seems to predispose to a larger weight gain in mothers.

Several association studies of type 2 diabetes mellitus (T2DM) and adiponectin gene polymorphisms have been reported with conflicting results. Our aim was to search for the association of three polymorphisms (-11.391G>A, +45T>G, and +276G>T) in the adiponectin gene with T2DM and prediabetic quantitative traits in Polish Caucasians. The study groups comprised 495 unrelated T2DM cases and 435 controls. We compared the distribution of genotypes between study groups. In addition, genotype-quantitative trait analyses were also done in the controls. The study subjects were genotyped using the restriction fragment length polymorphism technique. The frequencies of the minor alleles were as follows: 10.6 versus 8.2% for -11.391G>A (p = 0.0722), 7.0 versus 8.0% for +45T>G (p = 0.48), and 15.5% in T2DM versus 19.8% in controls (p = 0.0145) for +276G>T, respectively. The difference for genotype distribution between the groups was statistically significant (p = 0.0247) for the +276G>T variant: 71.31 versus 62.99%, 26.46 versus 34.48% and 2.22 versus 2.53%, respectively, for GG, GT and TT. In quantitative traits analysis, the T allele of +276G>T was associated (p < 0.05) with lower insulin resistance (HOMA-IR, fasting insulin) among controls. Additionally, the A allele at position -11.391 was associated (p < 0.05) with higher insulin resistance (HOMA-IR, fasting insulin). In multiple regression analysis, all identified association remained significant after the inclusion in the model of gender, BMI and age. In addition, in this model, -11.391G>A and +276G>T were independently associated with T2DM. Finally, we conclude that the adiponectin gene polymorphisms are associated with T2DM and prediabetic quantitative traits in Polish Caucasians.

Objective: Mutations in the ABCC8 gene encoding the SUR1 subunits of the beta-cell K-ATP channel cause neonatal diabetes (ND) mellitus. We aimed to determine the contribution of ABCC8 gene to ND in Poland, to describe the clinical phenotype associated with its mutations and to examine potential modifying factors., Patients: The Nationwide Registry of ND in Poland includes patients diagnosed before 6 months of age. In total 16 Kir6.2 negative patients with ND, 14 permanent and 2 relapsed transient, were examined., Measurements: ABCC8 gene mutations were detected by direct sequencing. Mutation carriers' characteristics included clinical data and biochemical parameters. In addition, we performed the hyperinsulinaemic euglycaemic clamp and tested for islet-specific antibodies in diabetic subjects., Results: We identified two probands with permanent ND (one heterozygous F132V mutation carrier and one compound heterozygote with N23H and R826W mutations) and two others with relapsed transient ND (heterozygotes for R826W and V86A substitutions, respectively). One subject, a heterozygous relative with the R826W mutation, had adult onset diabetes. There were striking differences in the clinical picture of the mutation carriers as the carrier of two mutations, N23H and R826W, was controlled on diet alone with HbA(1c) of 7.3%, whereas the F132V mutation carrier was on 0.66 IU/kg/day of insulin with HbA(1c) of 11.7%. The C-peptide level varied from 0.1 ng/ml (F132V) to 0.75 ng/ml (V86A). We also observed a variable insulin resistance, from moderate (M = 5.5 and 5.6 mg/kg/min, respectively, in the two R826W mutation carriers) to severe (M = 2.6 mg/kg/min in the F132V mutation carrier). We were able to transfer two patients off insulin to sulphonylurea (SU) and to reduce insulin dose in one other patient. Interestingly, there was no response to SU in the most insulin resistant F132V mutation carrier despite high dose of glibenclamide. All examined auto-antibodies were present in one of the subjects, the V86A mutation carrier, although this did not seem to influence the clinical picture, as we were able to transfer this girl off insulin., Conclusion: Mutations in SUR1 are the cause of about 15% of Kir6.2 negative permanent ND in Poland. The clinical phenotype of SUR1 diabetic mutation carriers is heterogeneous and it appears to be modified by variable sensitivity to insulin.

Introduction: There is a paucity of Polish data describing the characteristics of and assessing treatment goals in patients with relatively newly diagnosed type 2 diabetes., Objectives: The aim of the study was to describe the baseline characteristics of patients with newly diagnosed type 2 diabetes, who participated in the ARETAEUS1 study, and to assess to what degree diabetic control criteria recommended by the Polish Diabetes Association clinical practice guidelines are met., Patients and Methods: This cross-sectional questionnaire-based study was conducted from January to April 2009. It involved patients of any age and gender, diagnosed with type 2 diabetes after January 1, 2007, and recruited by randomly selected physicians, both diabetologists and non-diabetologists., Results: We analyzed 1714 valid questionnaires from 333 physicians: 1150 from non-diabetologists and 564 from diabetologists. Mean age of patients was 60 years, mean body mass index -- 30.6 kg/m2, proportion of females -- 50%. The levels of median glycated hemoglobin (HbA1c), total cholesterol and triglycerides, mean low-density lipoprotein (LDL) cholesterol, as well as blood pressure were above the thresholds recommended in the guidelines (i.e., <6.5% for HbA1c, <4.5 mmol/l for total cholesterol, <2.6 mmol/l [or <1.8 mmol/l in patients with coronary heart disease (CHD)] for LDL cholesterol, <1.7 mmol/l for triglycerides, and <130/80 mmHg for blood pressure). Cardiovascular disease risk factors were common: hypertension was reported in over 75% of patients, lipid disorders in nearly 75%, CHD in 27% (previous acute coronary syndrome or stable CHD), previous stroke in 4%, and previous transient ischemic attack in 5.5%. Diabetic foot was reported in 1.7% of patients, nephropathy in 7%, retinopathy in 9% (in the group of diabetologists) and in 21% of patients (in the group of non-diabetologists)., Conclusions: We observed a relatively high prevalence of cardiovascular disease risk factors and late diabetes complications in patients with diabetes diagnosed within the previous 2 years.

Objective: 1,5-anhydroglucitol (1,5-AG) is a short-term marker of metabolic control in diabetes. Its renal loss is stimulated in hyperglycemic conditions by glycosuria, which results in a lowered plasma concentration. As a low renal threshold for glucose has been described in hepatocyte nuclear factor-1alpha (HNF-1alpha) maturity-onset diabetes of the young (MODY), the 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in patients with HNF-1alpha MODY and in type 2 diabetic subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1alpha MODY., Research Design and Methods: We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 type 2 diabetic patients and 47 nondiabetic control subjects. The 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). Receiver operating characteristic (ROC) curve analysis was used to evaluate 1,5-AG as a screening marker for HNF-1alpha MODY., Results: The mean 1,5-AG plasma concentration in diabetic HNF-1alpha mutation carriers was 5.9 microg/ml, and it was lower than that in type 2 diabetic patients (11.0 microg/ml, P = 0.003) and in nondiabetic control subjects (23.9 microg/ml, P < 0.00005). The ROC curve analysis revealed 85.7% sensitivity and 80.0% specificity of 1,5-AG in screening for HNF-1alpha MODY at the criterion of <6.5 microg/ml in patients with an A1C level between 6.5 and 9.0%., Conclusions: 1,5-AG may be a useful biomarker for differential diagnosis of patients with HNF-1alpha MODY with a specific range of A1C, although this requires further investigation. However, the clinical use of this particle in diabetic HNF-1alpha mutation carriers for metabolic control has substantial limitations.

Objective: Molecular background of diabetic retinopathy (DR) remains unknown. An interesting group of candidate genes encode proteins involved in insulin resistance., Aim: To search for association between the PPARgamma, calpain 10, PTPN1 genes and DR in type 2 diabetes mellitus (T2DM)., Methods: We examined 238 T2DM subjects without DR (NDR) and 121 with DR (mean diabetes duration: 9.1+/-6.8 and 15.1+/-7.7, respectively). The subjects were genotyped for four markers: Pro12Ala of PPARgamma, SNP43 of calpain 10, rs3787345 and rs754118 of PTPN1. The distributions of the genotypes were compared using the chi(2)-test and Fisher exact test., Results: The alleles and genotypes were not associated with DR in non-stratified analysis. To investigate the impact of T2DM duration, we performed analysis that excluded short duration NDR subjects and long-duration DR subjects. It allowed obtaining groups with similar T2DM duration but different DR status (DR: 88 individuals, 11.4+/-5.3 years; NDR: 136 individuals, 13.2 years+/-6.2, respectively). This analysis suggested that the alanine variant of Pro12Ala might be associated with decreased risk of DR (p=0.026 for alleles, p=0.038 and p=0.014 for genotypes in additive and dominant models, respectively). In multivariable logistic regression that included non-genetic parameters, Pro12Ala was not an independent risk factor (p=0.28). Further analysis showed, however, that Pro12Ala remained significant when urea level was excluded from the model., Conclusion: The alanine variant of the Pro12Ala polymorphism of PPARgamma might be associated with decreased risk of DR in T2DM. This effect may be indirect, at least in part, due to diabetic kidney disease.

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis. We report the significant improvement of diabetes control and quality of life in a CFRD patient using the sensor-augmented insulin pump. The system gives the patient the highest degree of flexibility, which is required in CFRD since food intake and activity levels vary widely from day to day, depending on the rapid changes of health status.

Apolipoprotein M (apoM) is a 26-kDa protein expressed mainly in the liver and kidneys. It is present predominantly in high-density lipoproteins (HDL). ApoM expression is influenced by the hepatocyte nuclear factor-1alpha (HNF-1alpha), which is a transcription factor associated with the pathogenesis of MODY. Some earlier data suggested that apoM levels were lower in the serum of HNF-1alpha MODY subjects, than in that of other diabetics and healthy controls. The aim of this study was to evaluate apoM as a biomarker for HNF-1alpha MODY. We included in this study 48 HNF-1alpha mutation carriers (40 diabetic patients and 8 subjects with normal glucose levels in the fasted state) from the Polish Nationwide Registry of MODY. In addition, we examined 55 T2DM patients and 55 apparently healthy volunteers who had normal fasting glucose levels. ApoM was measured by the sandwich dot-blot technique with recombinant apoM (Abnova) as a protein standard, mouse anti-human apoM monoclonal primary antibody and rat anti-mouse HRP-conjugated secondary antibody (BD Biosciences). Mean apoM level in the MODY group was 13.6 mug/ml, SD 1.9 (13.5 mug/ml, SD 1.7 in diabetic subjects and 13.9 mug/ml, SD 2.0 in non-diabetic mutation carriers respectively). In the T2DM group, mean apoM level was 13.7 mug/ml, SD 2.1, while it reached 13.8 mug/ml, SD 2.0 in healthy controls. There was no difference between apoM serum concentrations in all the study groups. In summary, our study showed no association between HNF-1alpha mutations resulting in MODY phenotype and apoM levels. Thus, we cannot confirm the clinical usefulness of apoM as a biomarker of HNF-1alpha MODY.

Activating mutations in the KCNJ11 gene encoding the ATP-sensitive potassium-channel subunit of Kir6.2 result in the phenotype of permanent neonatal diabetes (PNDM). Patients with PNDM can be successfully transferred from insulin to sulphonylurea. It is not clear, however, whether the type of diet may play a role in the metabolic control in PNDM patients. This report describes two cases of patients with PNDM due to the R201H mutation coming from the Polish Nationwide Registry of PNDM treated with the same sulphonylurea (glipizide GITS). In one of them, diet was practically free (Pol1), the other one (Pol2) avoided high glycemic-index products. Both mutation carriers were submitted to a 72 h continuous glucose monitoring system (CGMS) (Medtronic, CA). Before the CGMS record, families were encouraged not to alter their usual pattern of food intake during recording periods and to use food diaries. The postprandial glycemia in Poll reached the maximal level of 9.5 mmo/l, 5 episodes of glycemia above 8.0 mmol/l lasting overall for about 6 hours followed the ingestion of high-glycemic-index (>70) meals. Patient Pol2 did not use high-glycaemic-index-products and his postprandial blood glucose did not exceed 7.0 mmol/l. Following the CGMS record, an additional diet-oriented educational session with patient Poll and his parents was performed, Poll declared to avoid the intake of high-glycemic-index products. He remained on the same dose of Glipizide GITS. Results of home blood glucose monitoring performed 2 months later showed normoglycemia. We conclude that to achieve normoglycemia, patients with PNDM who are on sulphonylurea should refrain from eating high glycemic-index products.

Maternally inherited diabetes with deafness (MIDD) is a rare, monogenic form of diabetes mellitus caused by mutations in the mitochondrial genome, the most frequent being the A3243G substitution of the tRNA(Leu) gene. We screened 520 individuals with type 2 diabetes mellitus and 45 probands from families with a clinical picture of maturity onset diabetes of the young (MODY) using restriction fragment length polymorphism. One carrier of the mutation being investigated was found in a proband from a MODY family. The patient was a 20 year-old woman, diagnosed at the age of 16 years as having type 1 diabetes mellitus. On entry to the study, she was treated by a multiple daily injection regimen (MDI) with regular human insulin and human NPH insulin. Typical extra-pancreatic symptoms of MIDD were present, such as macular pattern dystrophy and mild bilateral sensory hearing loss. Additionally, the patient presented abdominal obesity (BMI 32.0), an uncommon feature in monogenic insulin secretion defects, including MIDD. To facilitate weight loss, the diabetes treatment was modified. Since metformin treatment is considered to be contraindicated in MIDD because of the increased risk of lactic acidosis, we used insulin analogues (aspart and detemir) in an MDI regimen and hypocaloric diet. This resulted in a 6.3 kg weight reduction (BMI 27.4) and normalization of HbA1c level (from 7.2 to 6.1 %) during a three-month follow-up. On the basis of this case, we suggest that an MDI regimen with insulin analogues may be a preferred therapeutic option in some rare clinical situations, such as MIDD associated with obesity.

The K121Q polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is associated with type 2 diabetes and obesity. The possibility of other ENPP1 polymorphisms influencing these phenotypes has received little attention. Our aim was to examine the associations of tagging single nucleotide polymorphisms (SNPs) and haplotypes of the linkage disequilibrium (LD) block containing K121Q polymorphism with type 2 diabetes in a Polish population, controlling for any effect of obesity. We genotyped 426 type 2 diabetic case and 370 control subjects for seven SNPs in ENPP1. In the total group, neither type 2 diabetes nor obesity was significantly associated with any SNP. However, in obese subjects, two SNPs were significantly associated with type 2 diabetes: the Q allele of K121Q (odds ratio 1.6 [95% CI 1.003-2.6]) and T allele of rs997509 (4.7 [1.6-13.9]). In the LD block, four SNPs plus the K121Q polymorphism distinguished six haplotypes, three of which carried the Q allele. Interestingly, the T allele of rs997509 sufficed to distinguish a 121Q-carrying haplotype that was significantly more associated with type 2 diabetes than the other two (4.2 [1.3-13.5]). These other two 121Q-carrying haplotypes were not associated with type 2 diabetes. In conclusion, we found a new SNP, rs997509, in intron 1 that is strongly associated with risk of type 2 diabetes in obese individuals. The molecular mechanisms underlying this association are unknown.

Familial LCAT deficiency (FLD) is a rare genetic disorder associated with corneal opacities, anaemia and proteinuria with renal failure. Here we report detailed analyses on plasma lipids, lipoproteins, and the molecular defect in two siblings from a Polish family presenting classical symptoms of FLD and their family members with newly discovered Val309Met mutation in exon 6 of LCAT gene. Both patients displayed low total (2.19 and 2.94 mmol/l) and HDL-cholesterol concentrations (0.52 and 0.48 mmol/l), low percentage of cholesteryl esters (CE) (11.1 and 12%), and decreased apo AI and apo AII serum levels. Low LDL-cholesterol, apo B and Lp(a) levels, and increased oleate/linoleate ratios in CE could be of importance in the development of atherosclerosis in these patients with low HDL-cholesterol. LCAT activity was 10% of normal, alpha-LCAT activity was 0, and LCAT concentration was undetectable by immunoassay. Plasma CETP activity was at lower limits of normal. PCR and sequence analysis of DNA from the proband and affected brother revealed a novel G-->A mutation in exon 6 of LCAT gene, which resulted in an amino acid substitution of valine for methionine (Val309Met). The proband and affected brother were both homozygous carriers, while the mother, siblings and children of patients were heterozygous carriers of a newly discovered mutation. This is the first LCAT mutation described in the Slavic population.

Activating mutations in the KCNJ11 gene encoding the Kir6.2 subunit of ATP-sensitive potassium channel have been described in patients with permanent neonatal diabetes mellitus (PNDM). The main pathophysiological feature of PNDM associated with Kir6.2 mutations is a profound defect in insulin secretion. However, the expression of Kir6.2 protein is not limited to beta-cells; it also includes skeletal muscles, heart, brain, and peripheral nerves. Thus, the hypothesis that Kir6.2 mutations may influence insulin sensitivity in humans seems justified. Moreover, this notion is additionally supported by an animal model of Kir6.2 knock-out mice. Four adult carriers of a Kir6.2 mutation from the Polish population (mean age 31.5 years, range 20-50) were available for this study that aimed to evaluate their insulin sensitivity by the hyperinsulinemic euglycemic clamp technique. Three subjects carried the R201H mutation and one patient was a carrier of the K170N mutation. In addition, eight healthy volunteers with normal glucose tolerance were examined for comparison (mean age 31.0 years, range 20-41). The mean M value, i.e. the amount of metabolized glucose, for PNDM cases equaled 4.49 mg/(kg x min) (range 2.76-6.66) and was significantly lower than in the control group (9.64 mg/(kg x min), range 4.59-18.00). This observation suggests that impaired insulin sensitivity, in addition to profoundly decreased insulin secretion, contributes to the clinical picture of PNDM resulting from mutations in the Kir6.2 gene. An additional factor that might influence insulin sensitivity in our diabetes patients is glucose toxicity that may have appeared due to poor metabolic control prior to the examination (mean HbA1c = 8.95%). The intriguing question to be answered in the future is whether an improvement in insulin action could be seen following the transfer of Kir6.2 mutation carriers to sulphonylurea compounds.

Fetuin A and matrix GLA protein--MGP are known as extraosseus calcification inhibitors. The aim of the study was to assess the dependence between metabolic status and fetuin A and matrix GLA protein levels in type 1 diabetic patients without ischaemic heart disease. The study was performed in a group consisting of 35 patients with type 1 diabetes mellitus (22 women and 13 men). Mean age of the studied group equaled 38.8 +/- 11.24 years, duration of diabetes mellitus 20.77 +/- 10.11 years. Fetuin A significantly correlated with HDL-cholesterol (r = 0.45; p = 0.007). Total cholesterol, LDL-chol and triglicerides correlated with HbA1c (r = 0.40, p = 0.03; r = 0.41, p = 0.03 and r = 0.37, p = 0.05), HDL-chol significantly correlated with glucose level at the examination day (r = 0.52, p = 0.04). There were also positive correlations of trigliceride with uric acid (r = 0.47, p = 0.09) and cystatin C (r = 0.44, p = 0.02). There were no correlation of MGP with other examined parameters. Initial results of fetuin A and MGP levels in long-term type 1 diabetic patients without ischaemic heart disease draws attention to new parameters in macroangiopathy development.

Interleukin-18 (IL-18) is a proinflammatory pleiotropic cytokine playing a major role in the inflammatory cascade. It was written up for the first time in 1995 as a factor inducing interferon gamma in Kupffer cells, macrophages as well as T and B cells. Authors are presenting actual publications concerning usefulness in interleukin 18 determination in clinical diagnostics.

Unlabelled: Cardiovascular and renal complications among type 1 diabetic patients are predictive factors for sudden cardiac death and stroke. The aim of the study was to assess the prevalence of diabetic nephropathy and autonomic neuropathy in type 1 diabetic patients with and without diastolic dysfunction in echocardiographic examination. The study was performed in a group consisting of 37 patients with type 1 diabetes mellitus. Mean age of the study group equaled 37.24 +/- 10.85 years, duration of diabetes mellitus 21.3 +/- 9.55 years. All patients performed EKG, and cardiovascular autonomic test with ProSciCard according to Ewing battery. The following parameters were assessed: heart rate (HR), standard deviation of HR, RMSDD, VLF, LF, HF, deep breathing test, Ewing supine test and Valsalva maneuver. Systolic and diastolic function was assessed in echocardiography examination at rest. In all patients following laboratory parameters were assessed: HbA1c, total chol, LDL-chol, HDL-chol, triglicerides, uremic acid, glucose, albumin, creatinine, cystatin C, microalbuminuria., Results: mean heart rate in the examined group --78.38 +/- 15.54 /min, VLF--1.59 +/- 1.7; LF--4.22 +/- 1.51, HF--0.82 +/- 0.88, mean heart rate during deep breathing test --79.63 +/- 13.71, Ewing ratio--0.91 +/- 0.11. Cardiovascular autonomic neuropathy and diabetic neuropathy were diagnosed in 3 patients, these patients suffered also from proliferative retinopathy and diabetic nephropathy. The remaining group of 34 patients has normoalbuminuria. Calculated creatinine clearance according to Cockroft-Gault equation was 88.85 +/- 9.60 m/min, cystatin C concentration--0.97 +/- 0.22 ng/ml. In echocardiography exam, there were no abnormalities in systolic function, and diastolic dysfunction was diagnosed in 15 patients. Preliminary results showed that only the cystatin C level significantly differed patients with and without diastolic dysfunction in echocardiographic examination. Cystatin C could be the first sign of renal failure among these patients. Cardiovascular autonomic neuropathy and diabetic nephropathy were diagnosed only in 3 patients with left ventricular diastolic dysfunction in echocardiographic study.

Arterial compliance is a significant prognostic factor of cardiovascular risk. Elevated serum homocysteine level is related to increased oxidative stress and impaired endothelial function. The aim of the study was to evaluate factors influencing arterial compliance in patients with diabetes. We examined 30 patients with type 2 diabetes. In each patient we performed measurements of arterial compliance, blood pressure, serum lipids, glucose and homocysteine concentration and microalbuminuria. Serum lipids were determined by enzymatic methods, using Boehringer-Mannheim reagents, homocysteine levels by ELISA, using Bio-Rad reagents, HbA1c by HPLC method and microalbuminuria by immunonephelometric method. Arterial compliance assessment was based on measurements of pulse wave velocity (PWV), registered on femoral and carotid arteries (mean of 20 measurements), using automatic sensor (Fukuda) and Complior system. The mean age of patients was 62.2 +/- 8.1 years, BMI 30.0 +/- 3.4 kg/m2, waist to hip ratio (WHR) 0.9 +/- 0.09, mean diabetes duration 14.1 +/- 7.5 years, and HbA1c level 7.7 +/- 1.5%. Mean cholesterol, HDL-cholesterol and triglyceride serum concentrations were as follows: 5.7 +/- 1, 2 mmol/l; 1.32 +/- 0.43 mmol/ll and 1.8 +/- 1.0 mmol/l, and homocysteine levels 16.3 +/- 3.9 mmol/l. Arterial compliance significantly correlated with age (r = 0.52, p = 0.007), homocysteine concentration (r = 0.47, p = 0.015), WHR(r = 0.47, p = 0.015) and creatinine levels (r = 0.51, p = 0.016). The results of the study suggest that in patients with type 2 diabetes arterial compliance is associated not only with age but also with serum homocysteine levels and renal function parameters.

Background: Type 2 diabetes (T2DM) patients are characterized by a very high risk of cardiovascular diseases. Among the factors that are responsible for this phenomenon are abdominal obesity and hemostatic abnormalities., Aim of the Study: To examine the association of the markers of coagulation and fibrinolysis with the parameters of abdominal obesity and metabolic compensation in T2DM patients., Methods: 46 T2DM patients participated in the study: 24 men (mean age 61.1 +/- 7.9 years) and 22 postmenopausal women (mean age 62.6 +/- 8.7 years). In each patient the content and distribution of fatty tissue was measured by a dual energy X-ray absorptiometry method (DEXA). The central abdominal fat/gynoid hip fat (CAF/GF) ratio was calculated. The following hemostatic parameters were measured: fibrinogen (Fb), factor VII (fVII), antithrombin III (ATIII), C protein (pC), tissue plasminogen activator inhibitor (PAI-1) and alpha 2 antiplasmin (alpha2 AP). In addition, the biochemical indices of metabolic compensation were measured: HbA1c, glucose levels and lipids., Results: Patients of both genders were divided according to median CAF/GF ratio. The activity of PAI-1 was significantly higher in women with CAF/GF ratio >or= 0.88 as compared to those with CAF/GF < 0.88 (2.64 +/- 1.28 vs. 1.61 +/- 0.27 U/ml, p < 0.05). The activity of ATIII was significantly lower in men with CAF/GF ratio >or= 1.17, as compared to those with CAF/GF < 1.17 (105.10 +/- 10.02 vs. 113.42 +/- 10.72 %, p < 0.05). There was a significant correlation between the CAF/GF ratio and the activity of PAI-1 in women (r = 0.30, p < 0.05). In addition, in men the CAF/GF ratio was negatively correlated with ATIII activity (r = -0.44, p < 0.05). Multiple stepwise regression analysis demonstrated independent association between the CAF/ GF ratio and the activity of PAI-1 (p < 0.001), and between the CAF/GF ratio and the activity of alpha2 AP (p < 0.01). There was an independent association between the concentration of HbA1c and the concentration of Fb (p < 0.001) and between triglycerides and the activity of fVII (p < 0.01)., Conclusions: The results of our study show that the patients with T2DM and with higher markers of abdominal obesity measured by DEXA show fibrinolysis impairment and thrombinogenesis elevation compared to those with lower abdominal obesity markers. Independent factors determining hypercoagulation also include metabolic control and lipids. Hemostatic disorders place subjects with diabetes and abdominal obesity at risk of developing vascular complications.

Neuropathy, one of the most common diabetes complications, is characterized by highly variable clinical picture. It is not established what evaluation scheme should be applied in the assessment of patient regarding diabetic neuropathy. The validity of various laboratory tests in the diagnosis of diabetic neuropathy also remains unclear. This paper describes different clinical manifestations of diabetic neuropathy and presents the most important methods of assessment of patients with neuropathy suspected based on literature data and authors' observations. Authors highlighted the implications of different methods in diagnostic process. The most valid methods include physical evaluation, determination of vibration sensation and assessment of nerve conduction velocity. The autonomic functions tests have a special role allowing for the diagnosis of autonomic neuropathy.

Introduction: It has recently been shown that polymorphisms of some genes might influence the genetic susceptibility to complex, multifactorial forms of type 2 diabetes mellitus (T2DM). One of those genes is peroxisome proliferator activated receptor gamma (PPARgamma). The PPARgamma gene product is a nuclear hormone receptor that regulates adipogenesis and is a target for thiazolidinediones, medications enhancing sensitivity to insulin. The Pro12Ala amino acid variant of the PPARgamma2 isoform is associated with T2DM in several populations., Aims: (1) To determine the allele and genotype frequency of the Pro12Ala PPARgamma2 amino acid variant in a Polish population; (2) To search for the association of the Pro12Ala polymorphism with T2DM in the examined population., Methods: We included 644 individuals in this study: 366 T2DM patients with age of diagnosis greater than 35 years and 278 non-diabetic control subjects. The fragment of the PPARgamma2 gene which contains the examined amino acid variant was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by the specific restriction enzyme BshI. Differences in distribution between the groups were examined by chi2 test., Results: The frequency of Pro/Ala alleles was similar in T2DM patients and in the control subjects (83.5%/16.5% vs. 84.5%/15.5%, respectively, P=0.607). Similarly, there was no difference between the groups when we analysed the genotype distribution. Stratification analyses based on age of diagnosis, body mass index (BMI), and family history of T2DM were performed. The Pro/Ala and Ala/Ala genotypes tended to be more frequent in T2DM cases with age of diagnosis >50 years than in controls (36.2% vs. 27.3%, P=0.046). This difference was not significant after Sheffe correction for multiple comparisons. The other stratification analyses did not show any difference between the groups., Conclusion: The frequency of the Pro12Ala PPARgamma2 polymorphism in the Polish population studied is similar to that in other Caucasian populations. In the case-control study, we were not able to confirm earlier reports that the Pro allele conferred an increased risk for development of T2DM. Moreover, the results of the stratified analysis suggest an opposite trend in late onset T2DM.

Background: Glucometry is an essential part of diabetes treatment, but so far, no standard quality control procedure verifying blood glucose meter results is available. In this study, we evaluated the analytical performance of eight glucose meters: GX and Esprit (Bayer Diagn.), MediSense Card Sensor, ExacTech (MediSense) with strips Selfcare (Cambridge Diagn), One Touch Basic, One Touch II, One Touch Profile (Lifescan) and Glucotrend (Boehringer Mannheim/Roche)., Methods: The evaluation included within-run imprecision, linearity, comparison with the laboratory method and calculation of differences between individual glucometers., Results: Within-run imprecision ranged from 1.5% to 4.5%, linearity assessed as the correlation between measured and calculated glucose concentrations yielded r(2) values from 0.97 to 0.981. Analytical bias of glucose concentration values obtained by the glucometry amounted from 0.14% to 16.9% of values measured by the laboratory method. Bias higher than 5% was found for One Touch Basic, II and Profile meters (however, glucose concentrations in plasma obtained by the laboratory method One Touch meters showed analytical bias from 3.0% to 8.8%). The regression analysis yielded slope values from 0.77 to 1.09 and r(2) values from 0.86 to 0.98. The best correlations with the laboratory method were found for One Touch Basic, II Profile, Glucotrend and Esprit meters. The calculated differences between the individual glucose meters can constitute 0.02-1.49 mmol/l (0.96-26.9%) at glucose concentration 5.55 mmol/l, and 0.16-4.16 mmol/l (0.96-24.96%) at glucose concentration 16.67 mmol/l. Error grid analyses have shown that Glucometers One Touch Basic and One Touch Profile yielded all results in zone A (acceptable). The remaining glucometers yielded 1-7% of results in zones B (insignificant errors), C or D (lack of detection and treatment)., Conclusions: All studied glucometers had both small deviation from laboratory reference values (<10%) and high concurrence with results obtained by the laboratory method.

Background: Hereditary hemochromatosis (HH) is characterized by excess iron deposition. Two mutations in the HFE gene are associated with HH. Heterozygous carriers of HFE mutations are at higher risk of developing type 2 diabetes mellitus (T2DM). The aims of our project were to identify the frequency of C282Y and H63D mutations in a population from the Małopolska region of south-eastern Poland, and to search for an association of HFE mutations with T2DM., Material/methods: We included 391 individuals in this study: 222 T2DM patients and 169 controls. Genotypes were determined by electrophoresis of the DNA digestion products from SnaBI and DpnII, respectively. Differences in distributions between the groups were then analyzed by the chi-squared test., Results: The frequency of wild/C282Y alleles was 98.2%/1.8% in T2DM patients and 96.7%/3.2% in controls (p=0.19). The frequency of wild/H63D alleles was 85.6%/14.4% and 88.8%/11.2% (p= 0.19), respectively. The distribution of genotypes was not statistically different. However, in stratified analyses based on age of T2DM onset and gender, we observed a higher prevalence of wild/H63D and H63D/H63D genotypes among T2DM patients diagnosed at > 49 years of age, the mean age for the entire group (p=0.018), and among male T2DM individuals (p=0.005) than in controls., Conclusions: The frequency of HH-associated mutations in this population from south-eastern Poland is similar to other Caucasians. We found no evidence for the association of the C282Y mutation with T2DM. The results do suggest, however, that the H63D mutation may play a role in the pathogenesis of late onset T2DM and in males in this Polish population.

Introduction: Chronic diabetic complications are the main problems in diabetology causing work unfitness, disability and premature death. Complete and homogenous assessment of diabetic complications is possible in hospitalised patients., Aim: Assessment of the occurrence of chronic diabetic complications and their risk factors in patients with type 1 diabetes mellitus (DMT1)., Material and Methods: Retrospective analysis included clinical data from 241 patients admitted to the Department of Metabolic Diseases CMUJ in Krakow, 159 women (age 29.76 +/- 9.7, diabetes duration 10.00 +/- 8.6) and 82 men (age 36.52 +/- 13.4, diabetes duration 11.78 +/- 11.08). We analysed the occurrence and risk factors of diabetic retinopathy, diabetic nephropathy, peripheral and autonomic neuropathy, diabetic foot syndrome and coronary artery disease (CAD). The following risk factors were considered: BMI, diabetic control (HbA, c), lipid profile, hypertension, smoking, alcohol consumption and family occurrence of cardiovascular diseases and diabetes., Results and Conclusions: The frequency of chronic diabetic complications was as follows: diabetic retinopathy 41.5%, peripheral polyneuropathy 29%, nephropathy 17%, cardiovascular autonomic neuropathy 8.7%, diabetic foot syndrome 8.3% and coronary artery disease 7.1% of patients. Half of retinopathic patients had peripheral polyneuropathy, at the same time retinopathy was the most frequent complication in patients with diabetic foot (90%), CAD (88.1%), nephropathy (85%), polyneuropathy (65.6%) and cardiovascular autonomic neuropathy (71.4%). Diabetic nephropathy was found in 70% with diabetic foot, in 58.7% with CAD, in 52.2% with cardiovascular autonomic neuropathy, in 41.5% with polyneuropathy and in 35% with retinopathy. The presence of diabetic foot was associated with the risk for co-occurrence of all the remaining diabetic complications. In CAD patients microangiopathy was much more frequent than the reverse relationship. All the complications except for CAD were more frequent in men with DMT1. Risk factors that correlated with all chronic diabetic complications were diabetes duration and arterial hypertension. Age, lipid abnormalities, smoking and alcohol consumption, family history were associated with varying degrees of DMT1 complications. In patients with microangiopathy, neuropathy and CAD the following components of metabolic syndrome were found: obesity, hypertension, dyslipidemia implying the contribution of insulin resistance to the pathogenesis of these complications.

Increased homocysteine and C-reactive protein (CRP) concentration is associated with increased coronary risk. The aim of the study was to assess the potential relationships between homocysteine and CRP levels and lipid coronary risk factors in men and women with diabetes. We examined 117 persons, 64 men and 53 women. Mean age of examined men was 62.0 +/- 8.1 yrs, mean diabetes duration 12.1 +/- 7.4 yrs, BMI 29.7 +/- 3.7 kg/m2; in women 60.6 +/- 8.1 yrs, 12.1 +/- 6.3 yrs and 31.8-4.9 kg/m2 respectively. Serum homocysteine and creatinine values were significantly higher in men than in women (15.3 +/- 4.7 vs 13.3 +/- 3.9 mumol/l and 93.6 +/- 19.8 vs 74.4 vs 17.2 mumol/l respectively), while HDL-cholesterol, fibrinogen and CRP levels were significantly higher in women than in men (1.28 +/- 0.5 vs 1.13 +/- 0.25 mmol/l; 3.53 +/- 0.5 vs 3.26 +/- 0.8 g/l and 4.7 +/- 3.2 mg/l vs 4.1 +/- 7.2 mg/l respectively). In men CRP concentration correlated significantly with BMI (r = 0.45, p < 0.01), fibrinogen (r = 0.42, p < 0.05) and HDL-cholesterol levels (r = -0.46, p < 0.01) I; in women it correlated with diabetes duration (r = 0.41, p < 0.01), BMI (r = 0.33, p < 0.05), WHR (r = 0.44, p < 0.01), postprandial glucose (r = 0.39, p < 0.05), HbA1c (r = 0.54, p < 0.010) and LDL-cholesterol concentration (r = 0.33, p < 0.05). Serum homocysteine was significantly associated with WHR (r = 0.39, p < 0.001) and creatinine (r = 0.26, p < 0.05) in men, while in women it also correlated with creatinine levels (r = 0.37, p < 0.01) and with age (r = 0.54, p < 0.001), HbA1c (r = 0.53, p < 0.01) and LDL-cholesterol levels (r = 0.31, p < 0.05). The results indicate the potential role of homocysteine and CRP level modification by influencing lipid levels and fat mass in patients with type 2 diabetes.

Experimental studies showed that calpain inhibitors suppressed post-ischaemic changes in the brain. We examined whether an association exists between variants of three single nucleotide polymorphisms (SNPs) -43, -19, and -63 in the calpain 10 gene and either stroke or size of ischaemic lesions on the CT in a Polish population. We included 209 patients with a first ischaemic stroke and 148 controls. The patients were divided into four groups based on the infarct size assessed on the CT taken within two week after stroke. Alleles of SNP19 were determined by electrophoresis of the PCR product on agarose gel by size; while for SNP43 and -63 the RFLP method was used. The allele frequencies for patients and controls were similar in both groups: SNP43- G/A- 73.5%/26.5% vs. 71.0%/29%, SNP19-three 32 bp/two 32 bp repeats--65.7%/34.2% vs. 62.2%/37.7%; SNP63- C/T- 89.5%/10.5% vs. 90.9%/9.1%, respectively. The distribution of the genotypes, haplotypes, and haplotype combinations did not differ in both groups. The distribution in the subgroups of patients based on the size of the ischaemic lesions was similar to controls. Our study did not showed any association between calpain 10 SNPs: -43, -19, and -63 and ischaemic stroke, or with the size of post-ischaemic cerebral lesions in a Polish population.

Polymorphisms of the genes involved in the metabolism of vitamin D may predispose to type 2 diabetes mellitus (T2DM). For example, there is evidence suggesting that vitamin D binding protein (DBP) amino acid variants at codons 416 (aspartic acid-->glutamic acid) and 420 (threonine-->lysine) may affect genetic susceptibility to T2DM. The aims of this study are: (1) to determine the allele, genotype, haplotype and haplotype combination frequencies of those DBP amino acid variants in a Polish population and (2) to examine their role in the genetic susceptibility to T2DM in a Polish population. Overall 393 individuals were included in this study: 231 T2DM patients and 162 controls. The sequence of DBP exon 11, which contains both examined variants, was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by specific restriction enzymes HaeIII and StyI. Since variants of DBP were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. Differences in distributions between the groups were examined by chi(2) test. At codon 416 the frequency of Asp/Glu alleles was 44.6/55.4% in T2DM patients and 40.7/59.3% in controls (chi(2)=2.1, d.f.=1, P=0.28). At codon 420 the frequency of Thr/Lys alleles were 69.4/30.6% and 71.6/28.4%, (chi(2)=0.41, d.f.=1, P=0.52), respectively. Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In conclusion, the frequency of amino acid variants at codons 416 and 420 of vitamin D binding protein gene in a Polish population is similar to other Caucasian populations, but differs significantly from other races. No evidence was found for an association between DBP frequent polymorphisms and T2DM in this population.

Objective: The polymorphisms of two genes have recently been associated with complex forms of type 2 diabetes mellitus (T2DM): calpain 10 and peroxisome proliferator-activated receptor-gamma (PPARgamma). Calpain 10 is a member of a large family of intracellular proteases. It was shown in Mexican-Americans and other populations that variants of three single nucleotide polymorphisms (SNPs), -43, -19, and -63, of this ubiquitously expressed protein influence susceptibility to T2DM. However, substantial differences were shown between ethnic groups in at risk alleles and haplotypes as well as in their attributable risk. Thus, it is important to determine the role of calpain 10 in various populations., Aim: To examine the role of calpain 10 SNPs -43, -19, and -63 in genetic susceptibility to T2DM in a Polish population., Methods: Overall, 377 individuals were examined: 229 T2DM patients and 148 control individuals. The groups were genotyped for calpain 10 SNP-43, SNP-19, and SNP-63. SNP-19 was examined by electrophoresis of the PCR product on agarose gel by size, while the restriction fragment length polymorphism (RFLP) method was used for the two other markers. Differences in allele, genotype, haplotype, and haplotype combination distribution between the groups were examined by chi(2) test., Results: Distributions of alleles, genotypes, and haplotypes at three loci defined by examined SNPs were not significantly different between the groups. However, the homozygote combination of 121 haplotype was more prevalent in the T2DM group than in the controls (17.9% vs 10.1%, P=0.039). No difference was observed in the 112/121 haplotype distribution. This heterozygous haplotype combination was associated with increased risk of T2DM in several populations., Conclusion: The results of our study suggest the association of calpain 10 121/121 haplotype combination created by SNPs -43, -19, and -63 with T2DM in a Polish population. However, we were not able to confirm the previously described role of the heterozygous 112/121 haplotype combination in susceptibility to T2DM.

It is difficult to establish predictors for diabetic neuropathy because no generally accepted criteria of its diagnosis exist. In previous investigations risk factors profiles for neuropathy differ markedly. The aim of this study was to assess risk predictors for diabetic neuropathy in relation to different criteria of its diagnosis. Ninety-five diabetic patients entered the study. The exclusion criteria included uremia, alcohol abuse and radiculopathy. Control group consisted of 43 healthy volunteers. All patients underwent the clinical assessment, instrumental evaluation of superficial and deep sensation, tests of cardiovascular autonomic function and nerve conduction studies. According to the performed assessment patients were classified into following groups: without neuropathy, suspicion of neuropathy, neuropathy confirmed in clinical examination, neuropathy confirmed in electrophysiological testing, autonomic neuropathy. Analysis showed that the most important predictors in patients with subjective symptoms were type 2 diabetes mellitus, diabetes duration and age of patients. When neuropathy was diagnosed according to the clinical examination, predictors included type 2 diabetesmellitus and duration of the disease. In the cases of neuropathy confirmed by electrophysiological studies and autonomic neuropathy, only diabetes duration appeared to be a significant predictor. Our study demonstrated that predictors for diabetic neuropathy varied in relation to different diagnostic criteria and where the most important predictor for all forms of neuropathy is duration of diabetes. This result indicates the need for frequent screening tests in patients with long duration of the disease, irrespective of its metabolic control, patients' age or type of diabetes.

Despite of dramatic improvement in diagnostic procedures and treatment of diabetic patients, cardio-vascular complications are still the most frequent causes of death in these patients. Diabetes influences myocardial and coronary vessels function by coexisting macroangiopathy, microangiopathy, metabolic disturbances and autonomic nervous system neuropathy. All these factors result in diastolic and systolic dysfunction of the heart. Cardiomyopathy, congestive heart failure and serious arrhythmias are the end stage of diabetic complications. Macroangiopathy demonstrates accelerated atherosclerosis (involving coronary arteries), which consequences can be observed in 1 type diabetes patients at around the age of 30. Causes of increased risk of macroangiopathy in type 1 diabetic patients are not clear. There are not many clinical, prospective trials which can allow for etiology determination of the increased incidence of atherosclerosis and mortality due to coronary artery disease in this population. Adding to traditional risk factors of atherosclerosis like genetic factors, hypertension, dyslipidemia, obesity, smoking and improper diet, other important risk factors are observed in diabetic patients. Only few clinical trials suggest that hyperglycemia, glycation, glycoxidation of proteins, lipoproteins, changes in their composition, microalbuminuria, coagulation, fibrinolytic disturbances are additional risk factors of endothelium dysfunction and atherosclerosis. Prevention and treatment of accelerated coronary artery disease and it's consequences are more complicated in the diabetic population than in others. Some of the clinical trials suggest that even improved glycemic control does not eliminate the elevated risk of coronary artery disease in type 1 diabetic patients.