Switching from Neutral Protamine Hagedorn (NPH) Insulin to Insulin Glargine 300 U/mL in Older and Younger Patients with Type 2 Diabetes: A Post Hoc Analysis of a Multicenter, Prospective, Observational Study.

INTRODUCTION: Older age and longer disease duration are key risk factors for hypoglycemia in patients with type 2 diabetes (T2D) who receive insulin. Previous studies have shown that insulin glargine 300 U/mL (Gla-300) improves glycemic control and reduces the risk of hypoglycemia, but whether this effect is observed in older patients switching from neutral protamine Hagedorn (NPH) insulin is unclear. METHODS: In this multicenter, observational study involving patients with T2D aged ≥ 18 years with glycated hemoglobin (HbA1c) ≥ 8%, we compared the safety and effectiveness of switching from NPH insulin to Gla-300 in subgroups of patients differing by age (< 65 vs. ≥ 65 years) and duration of diabetes (≤ 13 vs. > 13 years). RESULTS: A total of 469 participants were included in the study. From baseline to 6 months after switching to Gla-300, mean HbA1c decreased from 9.23% to 8.13% (p < 0.001) among patients aged ≤ 65 years (224 patients), and from 9.15% to 8.20% (p < 0.001) among those aged > 65 years (245 patients). The proportion of patients with ≥ 1 episodes of hypoglycemia decreased from 19.1% to 13.6% (p = 0.11) among those aged ≤ 65 years, and from 26.9% to 13.0% (p < 0.001) among those aged > 65 years; the reduction was significantly greater in those aged > 65 years (p = 0.001). The reduction in HbA1c was greater in those with a disease duration ≤ 13 years (p = 0.007), but the reduction in hypoglycemia was greater in those with a disease duration > 13 years (p < 0.0003). CONCLUSION: The switch from NPH insulin to Gla-300 improved glycemic control in older patients with T2D and in those with a longer disease duration. Older patients with T2D and those with a longer disease duration benefited even more from the switch to Gla-300 than younger patients and those with a shorter disease duration, with significantly greater reductions in the risk of hypoglycemia.

Switching from Neutral Protamine Hagedorn Insulin to Insulin Glargine 300 U/mL Improves Glycaemic Control and Reduces Hypoglycaemia Risk: Results of a Multicentre, Prospective, Observational Study.

Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality worldwide and is an important public health issue. A significant proportion of insulin-treated patients with T2DM do not reach target glycated haemoglobin (HbA1c) values, which ultimately increases their risk of long-term microvascular and macrovascular complications. One potential option to improve diabetes control in these patients may be the use of new insulin formulations including second-generation basal insulin analogues such as insulin glargine 300 U/mL (Gla-300). Several published randomised controlled trials have assessed the clinical effectiveness of Gla-300, mostly versus insulin glargine 100 U/mL as well as insulin degludec. However, there is limited information about the real-world effectiveness of Gla-300 when patients are transitioned directly from neutral protamine Hagedorn (NPH) human basal insulin. The primary objective of this study was to evaluate the effectiveness of Gla-300, defined as the percentage of participants with an HbA1c reduction of ≥0.5%, 6 months after switching from NPH insulin, in participants with T2DM. Secondary objectives included the safety assessment based on the percentage of patients experiencing ≥1 episodes and the number of hypoglycaemic episodes by category: severe, symptomatic, symptomatic confirmed, diurnal or nocturnal, change in body weight, and insulin dose. A total of 469 participants completed the 6-month observation period. Mean baseline HbA1c was 9.19%. The percentage of participants with a ≥0.5% improvement in HbA1c from baseline was 71.7% at 6 months. Mean HbA1c decreased at 3 and 6 months by 0.77% (±0.98) and 1.01% (±1.12), respectively (p < 0.00001 versus baseline), while fasting glycaemia decreased by 32 mg/dL and 37 mg/dL, respectively (p < 0.00001 versus baseline). There were moderate increases in the doses of both Gla-300 and, if used, short-acting insulins during the 6 months of observation. The percentage of participants with ≥1 hypoglycaemia event during the preceding 4 weeks decreased significantly from baseline to 3 and 6 months, as did the proportion with symptomatic hypoglycaemia at night (p < 0.00001 versus baseline). No participants had severe hypoglycaemia after a switch to Gla-300. Body mass, waist and hip circumferences, and waist : hip ratio did not change significantly. In conclusion, this large, prospective, observational study demonstrated that switching from NPH insulin to Gla-300 resulted in a significant improvement in HbA1c, with only a moderate increase in insulin dose, a decreased risk of hypoglycaemia, and no increase in body weight.

Pancreatic exocrine insufficiency is not common in HNF-1alpha MODY.

AIMS: Exocrine pancreatic insufficiency has been described in Type 1 and Type 2 diabetes. The hepatocyte nuclear factor (HNF)-1alpha gene associated with maturity-onset diabetes of the young (MODY3) is expressed in several organs, including the exocrine pancreas. The aim of this study was to determine the prevalence of exocrine pancreas dysfunction in HNF-1alpha MODY patients. METHODS: Thirty-one diabetic HNF-1alpha MODY patients (mean age 37.2 +/- 14.6 years) and 35 healthy control subjects (39.1 +/- 13.9 years) participated. In addition, 25 Type 1 diabetic (T1DM) subjects were also examined (mean age 30.6 +/- 10.1 years). Exocrine pancreas function was assessed by measurement of stool elastase 1 (E1) activity. All diabetic patients and control subjects completed a gastrointestinal (GI) symptoms questionnaire. RESULTS: In all but two individuals, stool E1 levels were normal (> 200 microg/g). The only case of severely impaired pancreas exocrine function (E1 = 47.5 microg/g) was observed in the MODY3 group. The mean stool E1 elastase level in the HNF-1alpha MODY group was significantly lower than in the control subjects (401.0 +/- 118.4 vs. 482.7 +/- 151.1 microg/g, P = 0.001). Similarly, E1 levels in T1DM were lower than in control subjects (344.8 +/- 132.1 microg/g, P = 0.001); one patient with a moderate enzyme decrease was identified in this group. In addition, more frequent GI complaints were reported by HNF-1alpha MODY patients when compared with control subjects and also with T1DM patients. CONCLUSION: Pancreatic exocrine insufficiency is not common in HNF-1alpha MODY diabetic patients, although their stool E1 levels are lower than in healthy control subjects.

Molecular background and clinical characteristics of HNF1A MODY in a Polish population.

PURPOSE: Knowing the molecular background of monogenic diabetes in affected individuals influences the clinical practice. Mutations in the HNF1A gene are the most frequent cause of MODY. The aim of the present study was to identify the genetic and clinical characteristics of HNF1A MODY in a Polish population, and the prevalence of diabetic complications and renal malformations. METHODS: We identified 47 families with the early-onset, autosomal-dominant form of diabetes that met the criteria of MODY. Mutation screening involved direct sequencing of the HNF1A gene. Patients' characteristics included clinical data, anthropometric measurements and biochemical parameters. The search for renal malformations involved ultrasound examination of all HNF1A mutation carriers. RESULTS: We identified 13 HNF1A MODY families and examined 56 mutation carriers, including 46 diabetic patients. The average HbA(1c) level among the diabetics was 7.5%. We identified diabetic retinopathy in 47.7% of the MODY patients, while diabetic nephropathy was present in 25%. In five HNF1A mutation carriers from three families, renal developmental malformations were identified, including one functioning kidney in two (3.6%) of them. CONCLUSION: This first systematic search for HNF1A mutations in a Polish population revealed that they are a frequent cause of MODY. In this population, HNF1A mutation carriers were characterized by a high prevalence of diabetic complications. In addition, renal developmental abnormalities were found in some mutation carriers.

Clinical usefulness of a bolus calculator in maintaining normoglycaemia in active professional patients with type 1 diabetes treated with continuous subcutaneous insulin infusion.

This observational study assessed metabolic control in young, active professionals with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) with or without the use of a bolus calculator. Eighteen patients aged 19 - 51 years with diabetes duration of 6 - 22 years were included; eight patients used a bolus calculator and 10 did not. Metabolic control was assessed by glycosylated haemoglobin (Hb(A1c)) measurements and blood glucose profiles. A continuous glucose monitoring system (CGMS) was also used by three patients from each group. Mean Hb(A1c) and fasting blood glucose levels were not significantly different between the two groups, but mean post-prandial blood glucose was significantly lower in bolus calculator users than non-users. The CGMS showed more blood glucose levels within the target range in bolus calculator users than non-users, but statistical significance was not achieved. In conclusion, a bolus calculator may help to improve postprandial blood glucose levels in active professional type 1 diabetes patients treated with CSII, but does not have a major impact on Hb(A1c) levels.

A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus.

AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. RESULTS: There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was -6.57 ± 7.34 mg/ml (p = 0.04). CONCLUSIONS: A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

Polymorphisms in the gene encoding hepatocyte nuclear factor-4alpha and susceptibility to type 2 diabetes in a Polish population.

Recently, several association studies of type 2 diabetes mellitus (T2DM) and the hepatocyte nuclear factor (HNF)-4alpha gene were reported with conflicting results. Our aim was to search for association between two polymorphisms of HNF-4alpha and T2DM in Polish Caucasians. The study groups comprised of 461 T2DM cases and 366 controls. Genotype-quantitative trait analyses were based on the oral glucose tolerance test (OGTT), glucose and insulin results, and comprised 310 glucose-tolerant subjects. All individuals were genotyped for two HNF-4alpha polymorphisms. The frequencies of the minor alleles were as follows: 19.2% in T2DM vs. 17.6% in controls for rs2144908; and 20.6% vs. 20.1% for rs4810424, respectively. The distributions of alleles, genotypes, and haplotypes of the HNF-4alpha polymorphisms did not differ between the study groups (lowest P = 0.41). None of the examined SNPs showed an association in control subjects with quantitative traits of fasting plasma glucose, fasting insulin, as well as plasma glucose and insulin 2 hours after glucose load in OGTT. We conclude that both examined polymorphisms in HNF-4alpha are not associated with T2DM and prediabetic phenotypes in Polish Caucasian study groups of this size.

Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients.

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.

Further evidence for a susceptibility locus for type 2 diabetes on chromosome 20q13.1-q13.2.

We previously reported suggestive linkage between type 2 diabetes and markers in a region on chromosome 20q using data from a collection of 29 Caucasian families in which type 2 diabetes with middle-age-onset was segregated as an autosomal-dominant disorder. To map more precisely the susceptibility locus (or loci) within this broad region, we increased the family collection and genotyped all families for additional markers, both within the critical region and spaced over the rest of chromosome 20. Altogether 526 individuals (including 241 with diabetes) from the total collection of 43 families were included in the study. All individuals were genotyped for 23 highly polymorphic markers. Positive evidence for linkage was found for a 10-cM region on the long arm of chromosome 20q13.1-q13.2 between markers D20S119 and D20S428. The strongest evidence in two-point as well as multipoint linkage analysis (P = 1.8 x 10(-5)) occurred at the position corresponding to marker D20S196. The individuals with diabetes in the seven most strongly linked families had high serum insulin levels during fasting and 2-h post-glucose load periods. We did not find any evidence for linkage between type 2 diabetes and any other region on chromosome 20. In conclusion, our larger and more comprehensive study showed very strong evidence for a susceptibility gene for insulin-resistant type 2 diabetes located on the long arm of chromosome 20 around marker D20S196.

Prevalence of Retinopathy in Adult Patients with GCK-MODY and HNF1A-MODY.

We aimed to assess the prevalence of diabetic retinopathy (DR) in adult patients with GCK-MODY and HNF1A-MODY in Poland and to identify biochemical and clinical risk factors associated with its occurrence.We examined 74 GCK mutation carriers, 51 with diabetes and 23 with prediabetes, respectively, and 63 patients with HNF1A-MODY. Retinal photographs, 12 for each patient, were done by a fundus camera. Signs of DR were graded according to the DR disease severity scale. Statistical tests were performed to assess differences between the groups and logistic regression was done for the association with DR.The mean age at examination was 34.5±14.8 and 39.9±15.2 in the GCK-MODY and HNF1A-MODY groups, respectively. Mild nonproliferative DR (NPDR) was found in one patient with the GCK mutation and likely concomitant type 1 diabetes, whereas DR was diagnosed in 15 HNF1A-MODY patients: 9 with proliferative, 3 with moderate NPDR and 2 with mild NPDR. In univariate logistic regression analysis in the HNF1A-MODY group, significant results were found for diabetes duration, fasting glycemia, HbA1c, arterial hypertension, age at the examination, and eGFR. The strongest independent predictors of DR in HNF1A-MODY were markers of glucose control: HbA1c (OR: 2.05, CL%95: 1.2-3.83, p=0.01) and glucose (p=0.006, OR: 1.40, CL%95: 1.12-1.83) analyzed in 2 separated models. Additionally, arterial hypertension independently predicted DR (OR: 9.06, CL%95: 1.19-98.99, p=0.04) in the model with HbA1c as glycaemic control marker.In conclusion, DR of any degree was not present in our GCK-MODY group, while in spite of young age almost every fourth subject with HNF1A-MODY showed signs of this complication.

Amino acid variants of the vitamin D-binding protein and risk of diabetes in white Americans of European origin.

BACKGROUND: Genetic variants of vitamin D-binding protein (DBP) have been reported to be associated, not only with diabetes, but also with prediabetic traits, in several populations. There are two known polymorphisms in exon 11 of the DBP gene that result in amino acid variants: at codons 416 GAT-->GAG (Asp-->Glu) and 420 ACG-->AAG (Thr-->Lys). OBJECTIVE: To examine the association of these polymorphisms with diabetes in white Americans of European origin. METHODS: We studied unrelated individuals: 181 with type 1 diabetes, 215 with type 2 diabetes, and 163 healthy controls. Exon 11 was amplified using polymerase chain reaction and the two alleles were determined by digestion with specific endonucleases: HaeIII and StyI, respectively. RESULTS: At codon 416, Asp/Glu allele frequencies were 45%/55% in patients with type 1 diabetes, 43%/57% in patients with type 2 diabetes, and 46%/54% in controls (chi(2)=0.69, 2 d.f., P<0.71). At codon 420, corresponding Lys/Thr frequencies were 27%/73%, 30%/70%, and 30%/70% (chi(2)=1.25, 2 d.f., P=0.53). Distributions of genotypes at both loci, and the haplotypes defined by the two loci, were also very similar in all groups. CONCLUSION: DNA polymorphisms in the DBP gene are not associated with diabetes in white Americans of European origin.

Association study of the vitamin D: 1alpha-hydroxylase (CYP1alpha) gene and type 2 diabetes mellitus in a Polish population.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a complex disease. Genetic and environmental factors cooperate together to form its clinical picture. Polymorphisms in genes involved in the metabolism of vitamin D may influence susceptibility to T2DM. One of them is the vitamin D 1alpha-hydroxylase (CYP1alpha) gene. In this study we searched for the association of two markers, one in its intron 6 and the another one located upstream from the 5' end of CYP1alpha gene, with T2DM in a Polish population. METHODS: Overall 522 individuals were included in this study: 291 T2DM patients and 231 controls. The sequences, which contain both examined variants, were amplified by polymerase chain reaction (PCR). The T-->C polymorphism in intron 6 was assessed by the dot-blotting method using P(32). Genotyping of the other variant in the 5' end of CYP1alpha gene was carried out by restriction fragment length polymorphism (RFLP) method. Since variants of both SNPs were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. The distribution of alleles, genotypes, haplotypes and haplotype combinations was compared between the groups by chi(2) test. RESULTS: The frequency of T/C alleles of the 5'end variant was 81.7%/18.3% in T2DM patients and 82.8%/17.2% in the controls (chi(2)=0.2, 1.d.f., p=0.65). For a T-->C polymorphism in intron 6 the frequency of alleles was 65.1%/34.9% and 67.5%/32.5% in T2DM patients and controls, respectively (chi(2)=0.413, 1.d.f., p=0.669). Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In stratified analysis, we observed that the T-C/T-T heterozygous haplotype combination was more prevalent in the subgroup of obese T2DM patients (BMI >=30) than in the controls (41.5% vs 28.6%, p=0.01). CONCLUSIONS: Vitamin D 1alpha-hydroxylase is not a major gene for T2DM in a Polish population. However, this gene may be associated with T2DM in subjects with obesity. Thus, to definitely determine the role of this gene in T2DM further studies are necessary in other populations using larger sample size.

The Ala45Thr polymorphism of BETA2/NeuroD1 gene and susceptibility to type 1 diabetes mellitus in caucasians.

It has recently been shown that mutations in BETA2/NeuroD1 are responsible for the development of type 2 diabetes mellitus (T2DM) in Caucasians. This gene is located near the IDDM7 region and one of its amino acid polymorphisms, Ala45Thr, has been associated with type 1 diabetes (T1DM) in Japanese and Danish populations. The aim of our study is to examine Ala45Thr for its role in T1DM in Caucasians. We used both population-based case-control analysis and family-based transmission/disequilibrium testing (TDT). Genotyping was carried out by the dot-blotting method using P32. Study subjects comprised 202 type 1 diabetes cases (mean age at diagnosis: 11.1 years, mean age at examination: 36.4 years) and 139 controls with normal fasting glucose. For the TDT study, allelic transmission was evaluated in 209 case family trios. The frequency of the Ala45 allele was 70.3 % in cases and 62.9 % in controls (p=0.04), and 47.5 % of cases were Ala45 homozygotes compared to 36.0 % of controls (p=0.03). The TDT component of the study did not achieve statistical significance. However, given the high frequency of this variant even among controls, exceptionally large data sets are needed to provide adequate power for this approach. Our case-control study suggests that the Ala45 variant of BETA2/NeuroD1 may be associated with T1DM in Caucasians (or in linkage disequilibrium with a causative variant). However, this finding should be confirmed by a much larger family-based study.

Vitamin D receptor gene polymorphisms and association with type 2 diabetes mellitus in a Polish population.

Vitamin D plays an important role in insulin secretion. There is also evidence that this steroid may influence the insulin sensitivity. Thus genes involved in its metabolic pathway have been regarded as good candidates for type 2 diabetes mellitus (T2DM). One of them is vitamin D receptor gene (VDR). Its multiple polymorphisms have been examined for the association with T2DM in several populations. Those studies did not provide clear answers about the role of VDR in this disease. The aim of the study was to search for the association of FokI, ApaI, BsmI, and TaqI polymorphisms of VDR gene with T2DM in a Polish population using a case-control study design. Overall, 548 individuals were examined: 308 T2DM patients and 240 control individuals. The study groups were genotyped for VDR FokI, ApaI, BsmI, and TaqI variants using the restriction fragment length polymorphism (RFLP) method. Since variants of ApaI, BsmI, and TaqI polymorphisms were in very strong linkage disequilibrium, three loci haplotypes could be assigned to phase-unknown individuals with a high degree of confidence. Differences in allele, genotype, haplotype, and haplotype combination distribution between the groups were examined by chi2 test. The VDR allele frequencies for T2DM patients and controls were as follows: FokI-F/f - 53.4 %/46.6 % vs. 55.2 %/44.8 %, BsmI-B/b - 34.4 %/65.6 % vs. 37.5 %/62.5 %, ApaI-A/a - 47.9 %/52.1 % vs 50.9 %/49.1 %, TaqI-T/t - 67.6 %/32.4 % vs. 62.7 %/37.3 %, respectively. There was no difference between the groups in allele frequency. Similarly, distribution of genotypes, three locus BsmI/ApaI/TaqI haplotypes and their combinations were similar in the groups. In conclusion, our study did not provide evidence for the association of four examined VDR polymorphisms with T2DM in a Polish population. We postulate that to fully determine whether the sequence differences in VDR gene are susceptibility variants for T2DM, additional studies in different populations are required in a large study group.

The Ala45Thr polymorphism of BETA2/NeuroD1 gene and susceptibility to type 2 diabetes mellitus in a Polish population.

The BETA2/NeuroD1 gene product is a transcription factor, a member of a helix-loop-helix (HLH) family that is specifically expressed in the endocrine pancreas. HLH and homeobox proteins are involved in the development and function of pancreatic islets cells. Mice homozygous for a targeted disruption of BETA2/NeuroD1 showed abnormal pancreatic islet morphogenesis and developed overt diabetes. Mutations in the NeuroD/BETA2 gene were linked to the development of type 2 diabetes (T2DM). The aims of the study were to determine the allele and genotype frequency of Ala45Thr polymorphism of BETA2/NeuroD1 in a Polish population and to examine the role of this amino acid variant in the genetic susceptibility to T2DM. We included 394 individuals into this study: 223 T2DM patients with the age at diagnosis above 35 years and 171 controls without a family history of T2DM. The fragment of the gene, corresponding to the Ala45Thr amino acid variant, was amplified by polymerase chain reaction. Alleles and genotypes were determined based on electrophoresis of the specific restriction enzyme EcoI57 DNA digestion products. Differences in distribution between the groups were examined by chi(2) test. The frequencies of the Ala and Thr alleles in T2DM patients (62% and 37.9%) were similar to those in the controls (65.5% and 34.5%; p=0.32). Similarly, there was no difference between the groups when we analyzed the genotype distribution (p=0.24). The stratification analysis based on family history of T2DM, obesity, and age of diagnosis did not show any difference between the groups. In conclusion, the frequency of Ala45Thr polymorphism in this studied Polish population is similar to its frequency in other Caucasians. We did not find evidence that the Ala45Thr polymorphism of BETA2/NeuroD1 played a role in the risk of T2DM in the examined Polish population.

[Apoptosis--from theory to practice]. / Apoptoza--od teorii do praktyki.

Apoptosis-programmed cell death--is a process which has long been neglected in clinical thinking. Now we realize that it offers an understanding of a number of pathological conditions which otherwise cannot be explained. Moreover the analysis of the highly specific mechanisms of programmed cell death might aid in the development of new treatment strategies. In this paper we give the examples of the importance of apoptosis in the selected fields of clinical medicine. The knowledge of apoptosis in oncology, cardiology, endocrine diseases and others has achieved the level which enables its practical use. This is why we believe that apoptosis should attract attention of clinical practitioners.

[Corrected QT interval and diabetic neuropathy of the cardiovascular system]. / Skorygowany odstep QT a neuropatia cukrzycowa ukladu sercowo-naczyniowego.

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.

[Reactive gastritis in patients with diabetics with dyspeptic symptoms]. / Odczynowe zapalenie czesci przedodzwiernikowej zoladka u chorych na cukrzyce z objawami dyspeptycznymi.

UNLABELLED: There is very few data on the prevalence of reactive gastritis (RG) in diabetes mellitus (DM). The typical histological findings in RG are foveolar hyperplasia, oedema with apparent diminution in glands, telangiectasia of lamina propria, a paucity of inflammatory cells. RG has been connected so far with a long term use of non-steroidal anti-inflammatory drugs (NSAIDs) or bile reflux, which is particularly frequent after cholecystectomy. RG is regarded as less frequently associated with the Helicobacter pylori (Hp) infection. The aim of the study was to define: 1. The prevalence of RG in diabetics with dyspeptic symptoms as compared with the non-diabetic group. 2. The prevalence of Hp infection in RG as compared with chronic active gastritis (CAG) in DM. 3. The association of these types of gastritis with autonomic neuropathy (AN). STUDY DESIGN: Gastroscopy was performed in 152 patients with symptoms related to upper alimentary tract disorders-52 with DM (13 with IDDM and 39 with NIDDM) and 100 without DM. The presence of RG, CAG and Hp infection was analysed in 3 biopsies. AN was evaluated in 35 diabetics in 4 cardiovascular tests using ProSciCard. RESULTS: RG was significantly more frequent in DM than in control group (10/52, 19.2% vs. 3/100, 3%, respectively, p < 0.01). This difference was preserved after excluding all patients with NSAIDs use or being after cholecystectomy (8/36, 22.2% vs. 2/81, 2.5%, respectively, p < 0.001). Hp infection in diabetics with RG was significantly lower than diabetics with CAG (2/10, 20% vs. 16/23, 69.5%, respectively, p < 0.05). AN was more frequent in diabetics with RG than with CAG (7/10, 70% vs. 6/15, 40%, respectively, p < 0.001). Hp infection in diabetics with RG was significantly lower than diabetics with CAG (2/10, 20% vs. 16/23, 69.5%, respectively, p < 0.05). AN was more frequent in diabetics with RG than with CAG (7/10, 70% vs. 6/15, 40%, respectively), the difference was not significant with this sample size. CONCLUSIONS: 1. RG seems to be more frequent in DM than in general population. 2. Hp infection is less frequent in RG than in CAG in DM. 3. The higher prevalence of RG in DM may result from impaired motility and reflux of bile caused by AN.

The influence of dietary carbohydrate content on glycaemia in patients with glucokinase maturity-onset diabetes of the young.

Mutations in the glucokinase (GCK) gene result in maturity-onset diabetes of the young (MODY). Pharmacotherapy is not effective in GCK MODY. Thus, nutritional intervention seems to be the only therapeutic option. This study evaluated the effect of the quantity of dietary carbohydrate on glucose levels in 10 GCK mutation carriers: seven with MODY and three with prediabetes. All patients were exposed to high-carbohydrate diets for 2 days and then switched to low-carbohydrate diets (60% versus 25% of the daily calorie intake) for another 2 days, after a 1-day washout. Glucose levels were assessed by continuous blood glucose monitoring. In patients with GCK MODY on high-carbohydrate diets, glucose levels were significantly higher, and more hyperglycaemic episodes occurred, compared with patients on low-carbohydrate diets. This short-term observational study suggested that diets with a modestly limited carbohydrate content may improve glycaemic control in patients with GCK MODY.