Relationship between TP53 and interleukin-6 gene variants and the risk of types 1 and 2 diabetes mellitus development in the Kermanshah province

Diabetes mellitus (DM) is a metabolic disorder that results from insufficient secretion or insulin resistance, or both. Insulin secretion deficiency leads to chronic hyperglycemia along with impaired metabolism of proteins, lipids, and carbohydrates. This study aimed to investigate the TP53 gene SNP (single nucleotide polymorphism) rs1042522 genotype and the interleukin-6 (IL-6) gene SNP rs1800795 genotype in DM and control groups. This study was performed on 70 patients with type 1 DM, 100 patients with type 2 DM without related complications, 66 control subjects for type 1 DM, and 95 control subjects for type 2 DM. The control groups were matched regarding age and gender and did not have a familial relationship with the patient groups. All the subjects were residents of Kermanshah, located in the western part of Iran. Polymorphisms of TP53 and IL-6 genes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Lipid profile, fasting blood glucose, and HbA1c were measured using the ELISA and immunoturbidometric methods. The frequency of genotypes (CC, CG, GG) of the TP53 gene codon 72 in type 1 DM and its control group were significantly different (P= 0.013). Likewise, the frequency of genotypes (CC, CG, GG) of the TP53 gene codon 72 was significantly different between type 2 DM and control groups (P <0.001). The frequency of genotypes (GG, GC, CC) of G174C polymorphisms in the IL-6 gene was different between type 1 DM and control group as well as between type 2 DM and its control group, but it was not statistically significant. SNP rs1042522 genotypes in the dominant form (CG + GG vs. CC) (OR= 3.880; P < 0.001) and alleles G vs. C alleles (OR= 0.384; P < 0.001) increased the risk of type 2 DM significantly. There was no significant difference between type 1 and type 2 DM groups and respected control groups regarding the frequency of the IL-6 gene SNP rs1800795 alleles. The G allele of SNP rs1042522 encoding the TP53 gene increases the risk of developing DM in the population of the Kermanshah province, Iran.

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Hand functions in type 1 and type 2 diabetes mellitus

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh160328105a ◽

2017 ◽

Vol 145 (11-12) ◽

pp. 584-588

Author(s):

Pinar Akpinar ◽

Afitap Icagasioglu ◽

Esra Selimoglu ◽

Banu Mesci

Keyword(s):

Diabetes Mellitus ◽

Grip Strength ◽

Control Group ◽

Hand Functions ◽

Type 2 Dm ◽

Significant Difference ◽

Hand Disability ◽

Type 1 Dm

Introduction/Objective. Hand functions have an enormous impact on activities of daily living in patients with diabetes mellitus (DM), such as self-care, administering insulin injections, and preparing and eating meals. The aim of the study was to evaluate hand functions and grip strength in patients with type 1 and type 2 DM. Methods. This was an observational case-control study investigating the hand functions and grip strength in patients with type 1 and type 2 DM. The study comprised 41 patients with type 1 DM aged 25?50 years sex- and age-matched, 40 non-diabetic controls, and 91 patients with type 2 DM aged 40?65 years sex- and age-matched 60 non-diabetic controls. Patients with documented history of diabetic sensorimotor neuropathy and adhesive capsulitis were excluded. The Duruoz Hand Index was used to assess the functional hand disability. Grip strength was tested with a calibrated Jamar dynamometer. Results. The Duruoz Hand Index scores in patients with type 2 DM were significantly higher than in persons in the control group (p < 0.01), but there was no significant difference between the type 1 DM and the control group (p > 0.05). Grip strength values of patients with type 1 DM were significantly lower compared to those in the control group (p < 0.05), whereas there was no significant difference between patients with type 2 DM and their control group. There was a negatively significant correlation between grip strength and the Duruoz Hand Index scores in patients with both type 1 and type 2 DM (p < 0.05). Conclusion. Patients with type 1 DM and type 2 DM have different degrees of hand disability as compared to healthy control groups.

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The structural and functional features of the microcirculatory bed in patients with arterial hypertension and type 2 diabetes mellitus

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2005-11-3-177-180 ◽

2005 ◽

Vol 11 (3) ◽

pp. 177-180 ◽

Cited By ~ 1

Author(s):

L. A. Lohankova ◽

Yu. V. Kotovskaya ◽

A. S. Milto ◽

Zh. D. Kobalava

Keyword(s):

Diabetes Mellitus ◽

Blood Flow ◽

Arterial Hypertension ◽

Control Group ◽

Microcirculatory Bed ◽

Type 2 Dm ◽

Group A ◽

Functional Features

The structural and functional features of the microcirculatory heel (MCB) were studied in patients with arterial hypertension (AH) in relation to the presence or absence of type 1 diabetes mellitus (DM). Two hundred and twelve patients were examined. These included 110 patients with grades 1 and 2 arterial hypertension (AH) and type 2 DM, 82 patients with AH without type 2 DM, and 20 apparently healthy individuals. Laser Doppler flowmetry (LDF) was used to estimate basal blood flow, the loading test parameters characterizing the structural and functional status of MCB, and the incidence of hemodynamic types of microcirculation. Patients with AH concurrent with type 1 DM were found to have the following microcirculatory features: an increase in perfusion blood flow (microcirculation index, 8,8±1,8 perf. units versus 4,9±0,8 perf, units in patients with AH without DM and 6,7±0,9 perf. units in the control group), a drastic reduction in myogenic activity to 13,2±5,7 % versus 16,7±6,8 and 25,2±6,4 %, respectively, a decrease in vascular resistance, impairment of autoregulation, and low reserve capacities (reserve capillary blood flow was 197,8±31,6 % versus 429,9±82,01 % in the group of AH without DM and 302,8±50,1 % in the control group), a predominance of the hyperemic hemodynamic type (58,8 % in patients with AH and DM, 20,9 % in those with AH without DM, and 20,0 % in the controls). The specific features of the altered microcirculatory bed in patients with AH concurrent with type 2 DM were ascertained. These included the predominance of hyperemic microcirculation, impaired autoregulation. diminished microvascular resistance, and the low reserve capacities of the microcirculatory bed.

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Associations between Diabetes Mellitus and Nontuberculous Mycobacterium-Caused Diseases in Taiwan: A Nationwide Cohort Study

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1441 ◽

2021 ◽

Author(s):

Jui-Yang Wang ◽

Hsin-Chung Lin ◽

Hsin-An Lin ◽

Chi-Hsiang Chung ◽

Lih-Chyang Chen ◽

...

Keyword(s):

Diabetes Mellitus ◽

High Risk ◽

Cox Regression ◽

Nontuberculous Mycobacterium ◽

Research Database ◽

Cox Regression Analysis ◽

Type 2 Dm ◽

Type 1 Dm

Patients with diabetes mellitus (DM) are at greater risk of developing active tuberculosis and other intracellular bacterial infections, although the risk of acquiring infections from nontuberculous Mycobacterium (NTM) remains undefined. This study evaluated associations between DM and incidence of NTM infection-caused pulmonary and cutaneous diseases. Data for DM patients were extracted from the National Health Insurance Research Database of Taiwan. The DM cohort included 136,736 patients, and cases were matched randomly by age, gender, and index year with non-DM patients. Multivariate Cox proportional hazards regression was used to calculate adjusted hazard ratios of incident NTM-caused diseases in the DM cohort compared with non-DM control subjects. The frequency of incident NTM-caused diseases was significantly greater in DM patients (0.12%) than in non-DM patients (0.08%) (P < 0.05), including patients with type 1 DM (0.12%) and type 2 DM (0.12%) (all P < 0.05). Adjusted multivariate Cox regression analysis revealed that the incidence of NTM-caused diseases in DM patients was 1.43-fold greater than that in non-DM patients overall (P < 0.05), particularly in pulmonary (1.13-fold), other specific (excluding pulmonary, cutaneous, and disseminated diseases; 3.88-fold), and unspecific (atypical NTM infection; 1.54-fold) diseases (all P < 0.05). In conclusion, both type 1 DM and type 2 DM patients have high risk of NTM-caused diseases, suggesting that physicians need to pay more attention to this issue concerning the high risk of NTM-caused infection in DM patients.

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Activation of CD4+ and CD8+ T-lymphocytes by insulin and GAD in patients with type 1 or 2 diabetes mellitus

Endocrine Connections ◽

10.1530/ec-17-0230 ◽

2017 ◽

Vol 6 (8) ◽

pp. 758-765 ◽

Cited By ~ 2

Author(s):

Borros Arneth

Keyword(s):

Diabetes Mellitus ◽

T Lymphocytes ◽

Whole Blood ◽

Blood Samples ◽

Cd8 T Lymphocytes ◽

Type 2 Dm ◽

Whole Blood Samples ◽

Type 1 Dm

Background The origin of autoimmune disease type 1 diabetes is still unknown. Aim This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers. Materials and methods The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD. The analysis included samples from 12 type 1 DM patients, 14 type 2 DM patients and 12 healthy volunteers. Results Significant increases in the number of activated CD4+ and CD8+ T-lymphocytes following pre-incubation of whole blood samples with human insulin or GAD were observed in samples from patients with type 1 DM, whereas no activation of these cells was detected in samples from either type 2 DM patients or healthy subjects. Discussion These results indicated that latent pre-activation of CD4+ and CD8+ T-lymphocytes in response to insulin or GAD epitopes occurred in type 1 DM patients. Conclusion These findings suggest that pre-immunization against insulin and/or GAD might be associated with the development of type 1 DM. Alternatively, these results might reflect a non-specific, bystander autoimmune response.

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Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

Molecules ◽

10.3390/molecules25194381 ◽

2020 ◽

Vol 25 (19) ◽

pp. 4381

Author(s):

Zakiyatul Faizah ◽

Bella Amanda ◽

Faisal Yusuf Ashari ◽

Efta Triastuti ◽

Rebecca Oxtoby ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glucose Tolerance ◽

Diabetic Mice ◽

Β Cells ◽

Pancreatic Β Cells ◽

In Vivo Models ◽

Type 2 Dm ◽

Type 1 Dm

Diabetes mellitus (DM) is one of the major causes of death in the world. There are two types of DM—type 1 DM and type 2 DM. Type 1 DM can only be treated by insulin injection whereas type 2 DM is commonly treated using anti-hyperglycemic agents. Despite its effectiveness in controlling blood glucose level, this therapeutic approach is not able to reduce the decline in the number of functional pancreatic β cells. MST1 is a strong pro-apoptotic kinase that is expressed in pancreatic β cells. It induces β cell death and impairs insulin secretion. Recently, a potent and specific inhibitor for MST1, called XMU-MP-1, was identified and characterized. We hypothesized that treatment with XMU-MP-1 would produce beneficial effects by improving the survival and function of the pancreatic β cells. We used INS-1 cells and STZ-induced diabetic mice as in vitro and in vivo models to test the effect of XMU-MP-1 treatment. We found that XMU-MP-1 inhibited MST1/2 activity in INS-1 cells. Moreover, treatment with XMU-MP-1 produced a beneficial effect in improving glucose tolerance in the STZ-induced diabetic mouse model. Histological analysis indicated that XMU-MP-1 increased the number of pancreatic β cells and enhanced Langerhans islet area in the severe diabetic mice. Overall, this study showed that MST1 could become a promising therapeutic target for diabetes mellitus.

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Helicobacter pyloriInfection Is Associated with Type 2 Diabetes, Not Type 1 Diabetes: An Updated Meta-Analysis

Gastroenterology Research and Practice ◽

10.1155/2017/5715403 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 16

Author(s):

Jun-Zhen Li ◽

Jie-Yao Li ◽

Ting-Feng Wu ◽

Ji-Hao Xu ◽

Can-Ze Huang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Meta Analysis ◽

Cochrane Library ◽

Knowledge Database ◽

Type 2 Dm ◽

The Difference ◽

H Pylori ◽

Type 1 Dm

Background. Extragastric manifestations ofHelicobacter pylori(H. pylori) infection have been reported in many diseases. However, there are still controversies about whetherH. pyloriinfection is associated with diabetes mellitus (DM). This study was aimed at answering the question.Methods. A systematic search of the literature from January 1996 to January 2016 was conducted in PubMed, Embase databases, Cochrane Library, Google Scholar, Wanfang Data, China national knowledge database, and SinoMed. Published studies reportingH. pyloriinfection in both DM and non-DM individuals were recruited.Results. 79 studies with 57,397 individuals were included in this meta-analysis. The prevalence ofH. pyloriinfection in DM group (54.9%) was significantly higher than that (47.5%) in non-DM group (OR = 1.69,P<0.001). The difference was significant in comparison between type 2 DM group and non-DM group (OR = 2.05), but not in that between type 1 DM group and non-DM group (OR = 1.23, 95% CI: 0.77–1.96,P=0.38).Conclusion. Our meta-analysis suggested that there is significantly higher prevalence ofH. pyloriinfection in DM patients as compared to non-DM individuals. And the difference is associated with type 2 DM but not type 1 DM.

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Study of cutaneous manifestations of type 2 diabetes mellitus

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20175544 ◽

2018 ◽

Vol 4 (1) ◽

pp. 8

Author(s):

Yoganand J. Phulari ◽

Vidisha Kaushik

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Age Group ◽

Cutaneous Manifestations ◽

Skin Manifestations ◽

Type 2 Dm ◽

Type 1 Dm

Background: Poorly controlled Type 2 diabetes mellitus (DM) is associated with several disorders and microvascular, macrovascular and neuropathic complications. Multiple factors play a role in the manifestations of cutaneous signs of DM. The prevalence of a cutaneous disorder appears to be similar between Type 1 DM and Type 2 DM patients, but Type 2 DM patients develop more frequent cutaneous infections, and Type 1 DM patients manifest more autoimmune-type cutaneous lesions. The objective of the study was to assess the various cutaneous manifestations of Type 2 DM and the relation of cutaneous manifestations with the duration of Type 2 DM.Methods: All patients of Type 2 DM, of age group 20 and above, of both sexes, attending OPD or IPD at Dr. D. Y. Patil Hospital, Kolhapur willing to give written informed consent, were included for the study between August 2014 – July 2016. Complete history and examination of all the patients with regards to onset of cutaneous manifestations was taken.Results: Majority (49%) of respondents were in the age group of 41 to 60 years, and majority (66%) were males. 57.5% were new cases and 42.5% were known cases. Duration of illness- majority 50.58% were <5 years, 27.05% in 6 to 10 years. In present study there were 61% who had infectious skin manifestations and 39% who had non-infectious skin manifestations. Out of infectious manifestations 39.5% had fungal infection. Conclusions: Therefore on the basis of present study, we conclude that the skin is involved in DM quite often. The manifestations are numerous and varied and many a times they can serve as diagnostic marker for underlying DM. Whenever patients present with multiple skin manifestations, their diabetic status should be checked. The recognition of these skin findings is the key to treatment and prevention.

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Blood concentrations of endothelin, interleukins 6 and 10 in men with diabetes mellitus

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY ◽

10.22141/2224-0721.17.4.2021.237340 ◽

2021 ◽

Vol 17 (4) ◽

pp. 280-286

Author(s):

E.V. Luchytskiy ◽

V.E. Luchytskiy ◽

G.A. Zubkova ◽

V.M. Rybalchenko ◽

I.I. Skladanna

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Correlation Coefficient ◽

Blood Concentration ◽

Positive Correlation ◽

Type 2 Dm ◽

Type 1 Dm ◽

Spearman’S Correlation

Background. Pathological activation of cytokines is one of the key links in the pathogenesis of diabetes mellitus (DM) and the development of its complications, in particular from the cardiovascular system. According to the vast majority of researchers, the imbalance of pro- and anti-inflammatory cytokines in patients with diabetes mellitus is a significant risk factor for mortality from cardiovascular disease. The purpose of the study was to determine the concentration of markers of a nonspecific inflammatory response (interleukin (IL) 6 and IL-10) in the blood of men with DM and their association with glycated hemoglobin levels and body mass index. Materials and methods. There were examined 46 men with type 2 DM and 28 men with type 1 DM. According to the results of the analysis of variance of the control group, type 2 DM and type 1 DM had significant differences in some indicators. Results. The correlation analysis of the obtained indicators of interleukin concentration showed that in men with type 2 DM under the age of 50 years, the indicators of IL-6 concentration significantly positively correlated with indicators of IL-10 concentration in blood (Spearman’s correlation coefficient 0.562, p < 0.031) and negatively with the duration of diabetes mellitus (Spearman’s correlation coefficient –0.508, p < 0.031). In the group of patients with type 2 DM aged 50 years and older, there was a positive correlation between the blood concentration of IL-6 with the blood concentration of IL-10 (Spearman’s correlation coefficient 0.509, p < 0.031), the blood concentration of IL-10 with glycated hemoglobin levels (Spearman’s correlation coefficient 0.391, p < 0.04) and the duration of diabetes mellitus (Spearman’s correlation coefficient 0.551, p < 0.005). In the group of patients with type 1 DM, there was a positive correlation of IL-6 in the blood with indicators of the blood concentration of IL-10 (Spearman’s correlation coefficient 0.707, p < 0.001) and a positive correlation between the concentration of IL-10 with the duration of DM (Spearman’s correlation coefficient 0.379, p < 0.039). Conclusions. Mean levels of IL-6 were significantly elevated in men with type 2 diabetes aged 50 years and older. Mean IL-10 levels were significantly elevated in men with type 2 diabetes regardless of the age of the patients. A significant positive correlation was found between the indicators of IL-6 and IL-10 in the examined patients with type 2 diabetes regardless of age also in patients with type 1 diabetes mellitus.

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Diabetes mellitus in patients with rheumatoid arthritis in the Republic of Karelia

Modern Rheumatology Journal ◽

10.14412/1996-7012-2020-2-57-61 ◽

2020 ◽

Vol 14 (2) ◽

pp. 57-61

Author(s):

N. V. Koryakova ◽

I. I. Polskaya ◽

I. M. Marusenko ◽

T. I. Kulagina

Keyword(s):

Rheumatoid Arthritis ◽

Diabetes Mellitus ◽

General Population ◽

Late Onset ◽

Autoimmune Diabetes ◽

Type 2 Dm ◽

The Republic ◽

Type 1 Dm

Objective: to estimate the incidence of diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) in the Republic of Karelia and to analyze the types of carbohydrate metabolism disorders.Patients and methods. The investigation enrolled 889 patients aged 18 years and older with RA treated in the Rheumatology Department, V.A. Baranov Republican Hospital (Petrozavodsk), in 2000 to 2019. Among them, there were 709 (79.8%) women and 180 (20.2%) men; the median age was 59 [52; 66] years; the median duration of RA was 6.5 [1.75; 13] years. Most patients were found to have positive rheumatoid factor (68.3%), the second and more advanced radiological stages (90.6%), and moderate and high RA disease activity (84.8%). Methotrexate as a mainstay disease-modifying anti-rheumatic drug was taken by 68.2%; biological agents and glucocorticoids (GCs) were used in 4.8 and 3.3%, respectively. The incidence of DM and its types and risk factors (RFs) were analyzed.Results and discussion. DM was recorded in 67 (7.5%) RA patients (55 women and 12 men; the median age was 62 [56; 66] years). Among these patients, 9 (1.0%) patients with RA were observed to have type 1 DM, 50 (5.6%) and 8 (0.9%) patients had steroid-induced DM (SIDM), and type 2 DM, respectively. In 55.5% of cases, type 1 DM was represented by latent autoimmune diabetes in adults (LADA), which is of late onset. SIDM was detected in 75% of patients over 60 years of age who had RFs for type 2 DM. In this study, the incidence of type 2 DM in RA patients exceeded official figures in the general population of the Russian Federation, but was close to the predicted prevalence rates of type 2 DM. Patients with RA and type 2 DM had major RFs, such as age over 45 years, hypertension, overweight or obesity; moreover, 60% of patients were found to have a combination of these factors.Conclusion. RA patients showed a higher incidence rate of carbohydrate disorders of different types; the number of cases of type 1 DM and type 2 DM among the examined patients with RA exceeded that in the regional DM registries in the general population in the Republic of Karelia. It seems advisable to screen for carbohydrate disorders in patients with RA, especially in the presence of RFs for type 2 DM and during systemic therapy with GCs.

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Bioinformatic Analysis of Evolutional Conservatism and Functional Significance of Microsatellite Alleles of Human 14Q13.2 Region Associated with Type 2 Diabetes Mellitus

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/v10046-008-0001-6 ◽

2008 ◽

Vol 62 (3) ◽

pp. 91-102 ◽

Cited By ~ 1

Author(s):

Tatjana Sjakste ◽

Ilva Poudžiunas ◽

Valdis Pīrāgs ◽

Māris Lazdiñš ◽

Nikolajs Sjakste

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Functional Significance ◽

Bioinformatic Analysis ◽

Control Group ◽

Case Group ◽

Control Groups ◽

And Control ◽

Microsatellite Alleles

Bioinformatic Analysis of Evolutional Conservatism and Functional Significance of Microsatellite Alleles of Human 14Q13.2 Region Associated with Type 2 Diabetes Mellitus The paper deals with bioinformatic and statistical analysis of the possible functional significance of the previously shown association of several microsatellite alleles in intron 6 of the human proteasome core particle PSMA6 gene (HSMS006) and four other microsatellites localised upstream in human chromosome 14q13.2 (HSMS801, HSMS702, HSMS701, HSMS602) with type 2 diabetes mellitus in Latvia and Botnia, Finland. Genotype analysis revealed that (CAA)8/(CAA)8 homozygotes of the HSMS602 marker were never found in Type 2 diabetes patients, although 6.56% of the individuals from the control groups were the (CAA)8/(CAA)8 homozygotes. For the HSMS801 marker the (AC)21/(AC)23 genotype was never found in the case group and in the control group it was detected with a frequency 4.40%; these differences were statistically significant (P < 0.05). In contrast to the Latvian population, the distribution of genotype frequencies in cases and controls taken from the Botnian dataset was almost similar. Haplotype analysis showed that in the Latvian population besides haplotypes including alleles differently represented in case and control groups, a combination of some alleles almost equally represented in both groups formed combinations that were more characteristic of either the case group or the control group. This indicates probable independent functional significance of these haplotypes that warrants further investigation. In the Botnian population, more allele combinations were observed, and the distribution of haplotypes in case and control groups differed from that observed in Latvia. The observed haplotype distributions might reflect differences between the studied populations: a homogenous and isolated Botnian vis-à-vis a mixed Latvian population. Linkage disequilibrium (LD) analysis of data on the Latvian population revealed nine of ten two-allele combinations manifesting a high LD. HSMS006 and HSMS602 combination had a low LD; among the analysed markers these were situated at the largest distance from one another. Data on the Botnian population showed that haplotypes in eight of ten combinations had a high LD, including the HSMS006 and HSMS602 combinations. It appears that the two populations differ also in linkage disequilibrium of two-loci haplotypes. Theoretical analysis of a potential functional role of the polymorphisms indicated the significance of the microsatellite length of HSMS602 and HSMS006 for the formation of DNA hairpins. The whole genomic region appears to be conservative in mammals.

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