[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the main dietary factors influencing postprandial glycemia in typical type 2 diabetics, with the usage of a continuous glucose monitoring system CGMS ® Systems Gold (Medtronic MiniMed, Northridge, CA), and to determine postprandial glycemic patterns following ingestion of meals of different composition. Eight, obese individuals (BMI 31-34 kg/m 2 ) with type 2 diabetes, all treated with metformin, with good metabolic control, (HbA1c 140 mg/dl) was determined. An event was defined as a glucose value that persisted for at least 15 minutes.
Journal of diabetes science and technology 05/2008; 2(3):541-2.
[Show abstract][Hide abstract] ABSTRACT: Molecular background of diabetic retinopathy (DR) remains unknown. An interesting group of candidate genes encode proteins involved in insulin resistance.
To search for association between the PPARgamma, calpain 10, PTPN1 genes and DR in type 2 diabetes mellitus (T2DM).
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.
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.
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.
Diabetes research and clinical practice 05/2008; 80(1):139-45. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: We aim to assess serum total homocysteine (tHcy) associations with metabolic syndrome components and B-vitamins in women with gestational diabetes mellitus (GDM).
We studied 61 consecutive pregnant women, 44 with GDM and 17 with normal glucose tolerance (CG). Serum homocysteine levels were analyzed by ELISA, using Bio-Rad reagents. Serum folates and vitamin B(12) concentrations were determined by chemiluminescent immunoassay, free fatty acids (FFA) and lipids enzymatically.
Serum homocysteine levels were similar in both the GDM and the CG groups (8+/-2.0 vs 7.4+/-1.1 micromol/l, respectively). Women with GDM in comparison to CG women were characterized by higher values of homeostasis model of insulin resistance (HOMA-IR) (2.8+/-1.7 vs 1.6+/-0.9, P<0.01), serum triglycerides (2.7+/-0.9 vs 1.9+/-0.5 mmol/l, P<0.01) and FFA (0.6+/-0.2 vs 0.46+/-0.2 mmol/l, P<0.05). In GDM women serum tHcy correlated with vitamin B(12) (r= -0.47, P<0.01) and folates (r= -0.51, P<0.001); in CG women with HOMA-IR, a marker of insulin resistance (r= -0.49, P<0.05). In multiple regression analysis with serum tHcy as a dependent variable, folate and vitamin B(12) entered the analysis in GDM women (beta= -0.42 and -0.34, respectively, P<0.05), whereas in CG cystatin C and HOMA-IR entered the analysis (P<0.05).
In women with GDM, serum homocysteine is significantly associated with vitamin B(12) and folate levels, while in healthy pregnant women with HOMA-IR and with kidney function. The results suggest the importance of the B-group vitamins in regulation of serum tHcy levels in women with insulin resistance/gestational diabetes, what might be relevant in protection against pregnancy complications associated with elevated tHcy in GDM women.
Archives of Gynecology and Obstetrics 02/2008; 278(4):309-13. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the ability of atorvastatin, an HMG-CoA reductase inhibitor, to affect endothelial function and inflammation in long-duration (>10 years) type 1 diabetes mellitus (T1DM) patients without coronary heart disease (CHD) and arterial hypertension (AH).
We randomized 204 Caucasians with long-duration T1DM into either the atorvastatin 40 mg/day plus hypolipaemic diet group (n = 154) or the placebo plus hypolipaemic diet group (n = 50) for 6 months. Endothelium-dependent flow-mediated (FMD) and endothelium-independent flow-mediated vasodilatation, serum levels of plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) and high sensitivity C-reactive protein (hs-CRP) were estimated before and after treatment. After 6 months of therapy, FMD was increased by 44% in the atorvastatin plus diet group compared with the placebo plus diet group. Treatment with atorvastatin led to a significant reduction in levels of PAI-1 and hs-CRP; however, the elevation of vWF level was observed. In the placebo plus diet group, we observed a significant reduction in levels of hs-CRP but not of vWF and PAI-1.
Atorvastatin improves endothelial function and reduces some proinflammatory and prothrombotic markers of atherosclerosis in T1DM patients without CHD and AH. The surprising effect of atorvastatin on serum vWF levels in T1DM requires further study.
Diabetes Obesity and Metabolism 11/2007; 10(9):719-25. · 5.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, an association of Type 2 diabetes (T2DM) with polymorphisms in PTPN1 located on chromosome 20q was reported. We attempted to replicate this finding in an ethnically homogeneous Polish population.
The study groups comprised 474 cases with T2DM and 411 control subjects with normal fasting glucose. All individuals were genotyped for the five previously reported PTPN1 polymorphisms using a fluorescence polarization method. HAPLO.STAT software was used to infer and compare haplotype distributions.
The distributions of alleles and genotypes for the five genotyped PTPN1 polymorphisms did not differ between the T2DM cases and control subjects (lowest P = 0.6). Similarly, the frequency of the common haplotype reported to be associated with T2DM did not differ in cases and control subjects. We also failed to find such an association in Whites by performing a meta-analysis of all the available data on the association of those five SNPs with T2DM.
This case-control study in a Polish population did not confirm the reported association between polymorphisms in PTPN1 and T2DM.
Diabetic Medicine 06/2007; 24(6):650-5. · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
The Review of Diabetic Studies 02/2007; 4(4):231-5.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Evidence exists that some clinical, metabolic and genetic risk factors are associated with the development of diabetic retinopathy (DR). The aim of the study was: (1) to define the prevalence of DR in the examined group of 267 patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to identify in cross-sectional analysis, the clinical features associated with DR in the study group; and (3) to search for the association of 4 markers of vitamin D receptor (VDR), a candidate gene for vascular complications in diabetes, with DR. The examined group consisted of 146 female and 121 male T2DM patients (mean age at examination: 61.3+/-9.4 years; age at T2DM diagnosis: 50.0+/-9.2; T2DM duration: 11.3+/-7.8 years; body mass index (BMI): 30.5+/-5.5 kg/m(2); HbA1c: 7.8+/-1.5%). In all patients, the clinical and metabolic profile was determined. Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy after pupillary dilatation. Colour photographic documentation was made. The examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR polymorphisms based on the restriction fragment length polymorphism method. The statistical analysis was performed using univariate and multivariate logistic regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85 (31.8%) patients with T2DM. The multivariate analysis revealed that significant predictors of this complication were: never-smoking status (odds ratio 2.2, 95% confidence interval 1.2-4), urea serum level (1.3, 1.1-1.5), HbA1c level (1.4, 1.1-1.8) and insulin treatment (2.7, 1.4-5.1). Other features such as age of T2DM diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum creatinine level, albumin/creatinine ratio and arterial hypertension were univariate predictors of DR, however they lost significance as independent predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype and haplotype combination of VDR were not associated with the examined complication. However, there was a suggestion of a possible slight association between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that DR in T2DM patients remains a frequent complication in Polish T2DM patients. We were able to confirm the role of some clinical risk factors, surprisingly including not-smoking status, as was previously shown in the UK Prospective Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor for this size of study group.
[Show abstract][Hide abstract] ABSTRACT: 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.