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Macrosomia risk remains high in type 1 diabetes (T1DM) complicated pregnancies. A linear relationship between macrosomia risk and glycated hemoglobin A 1c (HbA 1c ) was described; however, low range of HbA 1c has not been studied. We aimed to identify risk factors and examine the impact of HbA 1c on the occurrence of macrosomia in newborns of T1DM women from a cohort with good glycemic control. In this observational retrospective one-center study we analyzed records of 510 consecutive T1DM pregnancies (1998-2012). The analyzed group consisted of 375 term singleton pregnancies. We used multiple regression models to examine the impact of HbA 1c and self-monitored glucose in each trimester on the risk of macrosomia and birth weight. The median age of T1DM women was 28 years, median T1DM duration-11 years, median pregestational BMI-23.3 kg/m 2 . Median birth weight reached 3520 g (1st and 3rd quartiles 3150 and 3960, respectively) at median 39 weeks of gestation. There were 85 (22.7 %) macrosomic (>4000 g) newborns. Median HbA 1c levels in the 1st, 2nd, and 3rd trimester were 6.4, 5.7, and 5.6 %. Third trimester HbA 1c , mean fasting self-monitored glucose and maternal age were independent predictors of birth weight and macrosomia. There was a linear relationship between 3rd trimester HbA 1c and macrosomia risk in HbA 1c range from 4.5 to 7.0 %. Macrosomia in children of T1DM mothers was common despite excellent metabolic control. Glycemia during the 3rd trimester was predominantly responsible for this condition., Competing Interests: The authors declare that they have no competing interests Ethical approval The study was conducted in accordance with the Declaration of Helsinki, and an independent ethics committee.

Hypoglycemic syndromes associated with immune reactions against insulin are rare phenomena described predominantly in Asians. Steroid therapy, immunosuppression or plasmapheresis is often required., Case Report: A 73-year-old White woman with a 20-year history of type 2 diabetes was admitted to hospital due to recurrent incidents of hypoglycemia that started several months after insulin initiation (lispro 75/25) and increased in severity over the next 5 years. They were accompanied by postprandial hyperglycemia up to 25 mmol/l. The patient’s glycated hemoglobin (HbA1c) was 70 mmol/ mol (8.6%). During hypoglycemic episodes recorded serum C-peptide was 0.57-0.73 nmol/l (1.7-2.2 ng/ml), while insulin concentration exceeded 7000 pmol/l (1000 mIU/l). Surreptitious insulin administration was ruled out as was, based on diagnostic imaging, the presence of an insulin secreting tumor. Anti-insulin antibody (AIA) level measured by 125I-insulin binding method was 92.5% (normal < 8.2%). Hypoglycemic episodes occurred for four days after discontinuation of insulin therapy and then resolved completely. Good glycemic control was maintained with metformin, acarbose and dapagliflozin. Three months later dapagliflozin was replaced with vildagliptine due to poor tolerance of a SGLT-2 inhibitor. Patient’s HbA1c was 54 mmol/mol (7.1%), total fasting insulin level 2577 pmol/l and AIA binding 85.9%. Over the next year the patient has not experienced hypoglycemia and maintained good glycemic control, as HbA1c level was 53 mmol/l (7.0%) and AIA binding 39.5%., Conclusions: In this rare case of a patient with diabetes and hypoglycemic syndrome related to AIA, we achieved a rapid and stable remission of hypoglycemia without immunosuppression. Good glycemic control, despite 20-year history of diabetes was achieved with oral hypoglycemic agents.

INTRODUCTION    Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with higher risk of complications. Strict glycemic control before conception reduces the risk of unfavorable outcomes. OBJECTIVES    The aim of the study was to assess changes in clinical characteristics, preconception treatment, and glycemic control of women with T1DM at the first antinatal visit. PATIENTS AND METHODS    We analyzed the records from the first antenatal visit of 524 women with T1DM in the years 1998-2012. The follow‑up period was divided into 3 5‑year periods. RESULTS    Differences in the age of patients between the 3 follow‑up periods were observed (28.2 ±5.7 years for 1998-2002; 27.3 ±4.5 years for 2003-2007; and 29.4 ±4.8 years for 2008-2012; P <0.0001). The number of women planning pregnancy did not change and reached 32.1% in the first, 44.4% in the second, and 40.4% in the third period (P = 0.2). The use of rapid‑acting insulin analogues increased from 2.6% to 46.5% and then to 95.6% (P <0.001). The rate of therapy with personal insulin pumps before pregnancy increased from 4.6% in the first, through 23.5% in the second, to 33.3% in the third period (P <0.001). Over the subsequent periods, we observed a decrease in hemoglobin A1c (HbA1c) levels at the first antenatal visit (from 7.4% ±1.6%, through 6.9% ±1.4%, to 7.0% ±1.4%; P = 0.06), as well as a decrease in HbA1c levels between the subgroups of women planning pregnancy (6.8% ±1.4%, 6.6% ±1.2%, and 6.1% ±0.8%, P = 0.015). CONCLUSIONS    In the years 1998-2012, an increase in the use of insulin analogues and personal insulin pumps by women with T1DM before conception was observed, and these changes were accompanied by a slight improvement in glycemic control, particularly among women planning pregnancy. The percentage of women planning pregnancy did not change during the follow‑up.

Cystatin C is a marker of glomerular filtration rate (GFR). Its level is influenced, among the others, by CRP whose concentration is decreased in HNF1A-MODY. We hypothesized that cystatin C level might be altered in HNF1A-MODY. We aimed to evaluate cystatin C in HNF1A-MODY both as a diagnostic marker and as a method of assessing GFR. We initially examined 51 HNF1A-MODY patients, 56 subjects with type 1 diabetes (T1DM), 39 with type 2 diabetes (T2DM) and 43 non-diabetic individuals (ND) from Poland. Subjects from two UK centres were used as replication panels: including 215 HNF1A-MODY, 203 T2DM, 39 HNF4A-MODY, 170 GCK-MODY, 17 HNF1B-MODY and 58 T1DM patients. The data were analysed with additive models, adjusting for gender, age, BMI and estimated GFR (creatinine). In the Polish subjects, adjusted cystatin C level in HNF1A-MODY was lower compared with T1DM, T2DM and ND (p < 0.05). Additionally, cystatin C-based GFR was higher than that calculated from creatinine level (p < 0.0001) in HNF1A-MODY, while the two GFR estimates were similar or cystatin C-based lower in the other groups. In the UK subjects, there were no differences in cystatin C between HNF1A-MODY and the other diabetic subgroups, except HNF1B-MODY. In UK HNF1A-MODY, cystatin C-based GFR estimate was higher than the creatinine-based one (p < 0.0001). Concluding, we could not confirm our hypothesis (supported by the Polish results) that cystatin C level is altered by HNF1A mutations; thus, it cannot be used as a biomarker for HNF1A-MODY. In HNF1A-MODY, the cystatin C-based GFR estimate is higher than the creatinine-based one.

Introduction and Objective: Continuous subcutaneous insulin infusion (CSII) via personal insulin pump is a valuable therapeutic tool in T1DM patients. However, adherence to recommended CSII-related behaviours may be of concern to young adults with intensive, variable daily activities (students, young professionals). The aim of this observational study was to estimate treatment outcomes in young adult patients with T1DM, and compare them with older individuals., Materials and Methods: Overall, 140 adults with T1DM on CSII were examined, divided into 2 subgroups: 77 patients younger than 26 years of age (mean 20.6 years) and 63 older subjects (mean 39.0). We compared the glycaemic control in both groups of T1DM subjects and analyzed treatment attitudes to identify potentially modifiable behaviours influencing the efficacy of the treatment., Results: The younger individuals were characterized by significantly worse treatment outcomes, compared to the older ones: the mean HbA1c levels were 7.6 ± 1.3% and 6.9±1.3% (p=0.00001), while the mean glucose levels based on glucometer downloads were 161±33.6 mg/dL and 136±21.8 mg/dL (p=0.00001), respectively. The frequency of self-monitoring of blood glucose (SMBG) was lower in younger individuals (5.3±2.1 vs. 7.0±2.8 daily, p=0.0005, respectively); they were also less frequently used advanced pump functions, e.g. the bolus calculator (48% vs. 67% users, p=0.0014, respectively)., Conclusions: The efficacy of CSII treatment observed in young T1DM adults was worse than in older patients. The reason for this phenomenon remains unclear, it may be due simply to age-dependend behaviours, to social environment, or both.

Sulfonylureas (SUs) were proven to be more effective than insulin in most Kir6.2 permanent neonatal diabetes mellitus (PNDM) patients. We report SU use during pregnancy in PNDM. A woman with the R201H Kir6.2 mutation became pregnant at the age of 37. The patient had been on glipizide 30 mg for 3 yr; her glycosylated hemoglobin level was 5.8%. She was diagnosed with chronic diabetes complications and a congenital defect of the urogenitary tract-a bicornuate uterus with septum. Because the effect of SU on fetal development is uncertain, she was switched to insulin after the pregnancy diagnosis; however, the subsequent glycemic control was unsatisfactory, with episodes of hyper- and hypoglycemia. Thus, in the second trimester, the patient was transferred to SU (glibenclamide, 40 mg), which resulted in stabilization of glycemic control; glycosylated hemoglobin in the third trimester was 5.8%. Prenatal genetic testing excluded the Kir6.2 R201H mutation in the fetus. A preterm cesarean delivery was carried out in the 35th week. The Apgar score of the newborn boy (weight, 3010 g; 75th percentile) was 8 at 1 min. He presented with hypoglycemia, transient tachypnea of the newborn, and hyperbilirubinemia. The recovery was uneventful. No birth defects were recorded. His development at the ninth month of life was normal. In summary, we show a high-risk pregnancy in long-term PNDM that despite perinatal complications ended with the birth of a healthy child. SUs, which seem to constitute an alternative to insulin during pregnancy in Kir6.2-related PNDM, were used during the conception period and most of the second and third trimesters.

Background: Recently, many patients with Kir6.2-related permanent neonatal diabetes mellitus (PNDM) have been successfully transferred from insulin therapy to sulfonylurea (SU) treatment. The long-term efficacy and safety of SU treatment in PNDM patients, however, have not yet been determined., Methods: We monitored glycemic control and the occurrence of potential side effects in 14 Kir6.2-related PNDM patients from Poland (median age, 12.0 years; range, 5-50 years) who were transferred to SU therapy at least 2 years ago. Three of the 14 patients were lost to follow-up, whereas for the remaining 11 individuals the median follow-up was 34 months (range, 27-51 months)., Results: The initial reduction of glycated hemoglobin (HbA1c) after the switch to SU (approximately 3-6 months post-transfer) was 1.68% (range, 0.3-3.7%), and good metabolic control was maintained over the entire period of observation with an average HbA1c level of 6.0% (range, 5.3-6.7%) at the last visit. This was accompanied by a substantial drop in SU dose by 0.24 mg/kg, which constituted a 38.0% decrease. A rapid progression of retinal changes was observed in one patient, a 34-year-old woman at the beginning of the observation, with preexisting proliferative diabetic retinopathy. No causal relationship between these changes and SU treatment could be proven. Neither serious side effects nor progression of diabetes complications was observed in any other patients. No detrimental effect on growth in the observed minors was recorded., Conclusions: In summary, the switch from insulin therapy to SU treatment in PNDM related to KCNJ11 mutations was found to be an efficient and safe therapeutic method over a period of 34-month median follow-up. Although no serious side effects were associated with SU treatment, their use in Kir6.2 PNDM requires further attention, particularly in children, adolescents, and patients with advanced chronic diabetes complications.

Cardiovascular autonomic function is measured as heart rate variability (HRV). The aim of the study was the HRV comparison between type 1 diabetic patients without (R0) and with diabetic retinopathy (R1). The group R0 was significantly younger (36.08 +/- 13.52 years) than group R1 (42.90 +/- 10.42 years). Diabetes duration was significantly longer in the group R1 as compared to group R0 (22.60 +/- 8.72 years vs 16.72 +/- 11.54 years, p < 0.04). Also HbA1c level in the group R1 was significantly higher as compared to the group R0 (p = 0.006). The data demonstrated that abnormal HR variability measured over a 24-h period provides information on the risk of sudden death. To assess HR variability twenty four hour EKG monitoring were performed in all examined patients. RR intervals were significantly longer between 2.00 a.m. and 5.00 a.m. In each hour of 24-h EKG Holter monitoring VLF and LF were significantly lower in the group R1. In the group R1 - HF was also significantly lower but only during sleeping time (between 11 p.m. and 7 a.m.). 24-h EKG monitoring is a useful and promising tool in diabetic patients with different microvascular complications.

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.

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.

Presented has been contemporary knowledge on diabetes gravidarum diagnosis and treatment.

Background: Genetics and environmental factors play a role in the pathogenesis of the complex disease, type 2 diabetes mellitus. Two major pathophysiological defects coexist in this disease: impairment of insulin secretion by beta-cells and decreased insulin sensitivity in peripheral tissues. The aim of the study was to examine whether two polymorphisms: the -308 G/A substitution in the promoter region of TNF-alpha gene and the K121Q amino acid variant of the PC-1 gene; influence insulin resistance in individuals with positive family history of type 2 diabetes mellitus., Methods: Sixty individuals were included into this study: 28 women and 32 men, all of them with normal glucose tolerance. Insulin and glucose serum levels were were assessed during the OGTT on fasting and at 30 and 120 minutes. Secondary indices of insulin resistance were calculated based on these measurements. Genotyping of the both examined polymorphisms was performed using the restriction fragment length polymorphism method (RFLP)., Results: Homozygous and heterozygous carriers of the A allele in position -308 of the TNF-alpha gene promoter showed higher plasma insulin levels at 120 min OGTT versus GG carriers (44.77 microliters/ml; SD 40.4 vs. 26.82; SD 19.9; p = 0.04) and a higher ratio of the 30 min increment in insulin to the 30 min increment in glucose (35.4; SD 21.5 vs. 22.6: SD 21.5; p = 0.03). In addition, homo- and heterozygous carriers of the Q allele at residue 121 of the PC-1 gene showed higher plasma glucose levels at 120 min OGTT compared to the KK subjects (5.38 mmol/l, SD 1.19 vs. 4.48, SD 1.11; p = 0.03)., Conclusion: Our study suggests that both examined polymorphisms: the -308 G/A in the promoter region of TNF-alpha and K121Q amino acid variant of the PC-1; influence the development of insulin resistance as a prediabetic quantitative trait in a Polish population.

A group of metabolic disorders including insulin resistance and hyperinsulinemia, impaired glucose tolerance, visceral obesity, hypertension, dyslipidemia, hyperuricemia, hypercoagulability and microalbuminuria determine the risk for the development of atherosclerosis, coronary artery disease and cerebral vascular disorders. Although available studies on the pathogenesis of the metabolic syndrome are equivocal, it is most frequently hypothesized that hereditary of insulin resistance leads to the remaining metabolic disorders including diabetes mellitus, atherosclerosis and coronary artery disease. Despite pathogenetic controversies, there are convincing arguments for the diagnosis of the metabolic syndrome and search for therapy improving insulin sensitivity and reducing hyperinsulinemia thus preventing the development of diabetes mellitus and coronary artery disease.

A case of Werner's syndrome has been reported. The patient presented with insulin resistance, non insulin dependent diabetes mellitus and muscular atrophy.

Unlabelled: Our objective was the analysis of the utility of the corrected QT interval (QTc) for the assessment of severity of cardiac autonomic neuropathy. Fourty nine patients with insulin-dependent diabetes mellitus/IDDM/were enrolled in the study. Their ages ranged between 16 and 58 years, and the duration of IDDM ranged between 1 and 38 years. Patients were tested for cardiac autonomic neuropathy using ProSciCard system. We carried out four tests: resting pulse deep breathing pulse Ewing test Valsalva maneuver Our results showed the relationship between the QTc interval lengthening and the occurance of cardiac autonomic neuropathy. No correlation was found between the QTc interval and the extend of cardiac autonomic neuropathy., Conclusions: The QTc interval measurement is a good routine test for the diagnosis of cardiac autonomic neuropathy. The corrected QT interval is not a reliable indicator of the extend of cardiac autonomic neuropathy.

The POL-MONICA Project screened in 1984 1309 men and 1337 women aged 35 to 64 years, inhabitants of Warsaw (the Warsaw centre) and 1250 men and 1472 women aged 35 to 64 years, inhabitants of the Tarnobrzeg province (the Cracow centre). In both environments the percentage of smoking men was similar (about 57%). Women from big city environment smoked three times more frequently (33.1%) than in the agricultural areas (10.7%). The smoking intensity was higher in the agricultural areas both among men and women. It has been stated that smoking habit depends on such social or demographic patterns as age, sex, civil state, education, physical activity related to work. Smoking influenced significantly the level of such risk factors as systolic arterial blood pressure, the fat body content in both men and women, and the HDL-cholesterol in women from both environments.