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Impaired circadian blood pressure (BP) variation (i.e. lack of nocturnal BP fall by at least 10% of daytime values; 'non-dipping') is associated with increased risk of cardiovascular events. Blunted circadian BP profile is common in hypertension and autonomic neuropathy as well as in patients with renal function impairment. However, pathophysiology of non-dipping phenomenon in normotensive diabetes subjects with normal autonomic function and without nephropathy is unclear. We studied whether angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism, known for its role in BP regulation, may play a role in 24-hour BP rhythm control. The study group comprised 34 normotensive normoalbuminuric type 2 diabetes patients with no signs of autonomic neuropathy (18 women, 16 men, mean [±SD] age 594±9 years, BMI 29.24-3.4 kg/m², diabetes duration 7.9±5.1 years, HbA[sub 1c] 8.6±1.4%) with impaired BP variation, the controls were 49 normotensive normoalbuminuric type 2 diabetes subjects (28 women, 21 men, age 624±10 years, BM1 30.3±3.9 kg/m², diabetes duration 8.5±3.1 years, HbA[sub 1c] 8.2±1.1%) with normal 24-hour BP rhythm. ACE I/D polymorphism as well as endothelial function and subclinical inflammation parameters (endothelin-1, sE-selectin, soluble intercellular (sICAM) and vascular (sVCAM) cell adhesion molecules, tumor necrosis factor-α (TNF-α) were assessed with ELISA in all the subjects. ACE DD genotype was found in 24 (71%) and ID in 10 (29%) study group subjects; 3 (6%) control subjects had DD, 32 (65%) - ID, and 14 (29%) - II genotype p<0.001). In the study and control group subjects fasting serum endothelin-1 was 7.9±:1.4 and 6.3±0.8 pg/ml (p<0.05), sE-selectin 28.9±12.2 and 18.2±12.7 ng/ml (p<0.05), ICAM 1569±732 and 755±473 ng/ml (p<0.01), VCAM 1932±556 and 1173±701 ng/ml (p<0.05), respectively. No statistically significant difference was found in serum TNF-α (85.7±83.3 and 82.8±73.3 pg/ml, p>0.05) between the groups. In conclusion, impaired circadian BP variation in normotensive normoalbuminuric type 2 diabetes patients is strongly associated with ACE DD genotype and marked endothelial dysfunction when compared to the subjects with normal BP rhythm. These findings may offer plausible explanation for the non-dipping phenomenon in normotensive normoalbuminuric type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Background: Human leukocyte antigens (HLA) complex and INS-IGF2 5'VNTR loci are principal determinants of the risk of type 1 diabetes mellitus (T1DM). Carriage of class III allele is protective, while class I/I homozygosity increases the risk of T1DM., Material and Methods: HLA and 5'VNTR allele frequencies were summarised and multivariate logistic regression models with interaction evaluation were employed to determine the presence and types of allele effect interdependency. The study group was planned to number 590 children who would undergo genotyping of 5'VNTR and HLA., Results: 590 patients (302 with T1DM and 288 controls) were recruited. Frequencies of HLA risk alleles were: 117 carriers of DR3-DQ2; 130 carriers of DR4-DQ8 including 43 DR3-DQ2/DR4-DQ8 heterozygotes. In all cases, risk alleles were vastly overrepresented in the T1DM group compared to the controls (p < 0.0001 in all cases). The most frequent protective haplotype was DQB1 × 0602 observed in 24 controls and two T1DM cases (p < 0.001). Class I 5'VNTR homozygotes constituted 58% of the control group (n = 174) and 78% (n = 224) of T1DM patients [OR = 2.63 (95% CI: 1.79-3.57)]. Interactions between 5'VNTR and DR3-DQ2 or DR4-DQ8 variants did not reach statistical significance for risk of developing T1DM (p = 0.54 and 0.24) or age at its diagnosis (p = 0.14 and 0.67 respectively)., Conclusions: Interactions between HLA and 5'VNTR genotype are not of multiplicative character. Class I homozygosity at 5'VNTR is a significant risk factor of T1DM and acts independently from HLA haplotype in determining the actual risk of diabetes in children.

Introduction: A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis., Aim of the Study: The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome., Material and Methods: 9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected., Results: In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome., Conclusions: Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.

Aim: The aim of the study was to evaluate an association between ACE genotypes and blood pressure (BP) disturbances in children and adolescents withType 1 diabetes mellitus., Materials and Methods: 126 normo-albuminuric, type 1 diabetic children and adolescents at the age 10.5-19.7 years, and duration of diabetes 2.0-17.8 years, were included in the study. All patients were clinically normotensive and normoalbuminuric. Twenty-four-hour ambulatory BP monitoring was undertaken in all patients. The values of systolic BP, diastolic BP, mean arterial BP blood pressure and diurnal variation in BP were estimated. Prehypertension was diagnosed as BP values between 90pc or 120/80 mmHg and 95pc. ACE genotypes were assessed using polymerase chain reaction., Results: In 48 individuals (38.1%) prehypertension was diagnosed. ACE genotypes distributed in patients were as follow: 31 (24.6%) genotype II, 45 (35.7%)--ID, and 50 (39.7%)--DD. Patients with DD genotype had higher nocturnal systolic BP (104 vs. 101 mmHg; p=0.029), diastolic BP (54 vs. 52 mmHg, p=0.003) and mean arterial BP (71 vs. 68 mmHg, p=0.003) as compared to carriers of the I allele (group ID + II). In the group DD in compare to the group ID + II lower nocturnal depletion in diastolic BP (18.0 vs. 20.5 mmHg, p=0.024) and mean BP (14.8 vs 16.6 mmHg, p=0.049) was observed. 14% patients of the DD group were non-dipper and 1.32% in the group ID + II (p=0.01). There was no differences in the prevalence of prehypertension between genotype groups (II+ID vs. DD: 38.2 vs. 38.0%, ns)., Conclusions: Genotype DD is associated with nocturnal BP abnormalities in normotensive and normo-albuminuric children and adolescents with type 1 diabetes. There is no relationship between frequency of prehypertension and ACE gene polymorphism.