Country-specific birth weight and length in type 1 diabetes high-risk HLA genotypes in combination with prenatal characteristics

Abstract Aims Alterations of the exocrine pancreas have been reported in type 1 diabetes, but their contribution to the pathogenesis of the disease is poorly understood. Here, we investigated markers of exocrine pancreas dysfunction in individuals at-risk of developing type 1 diabetes. Methods Serum P-amylase and lipase levels were assessed in samples obtained from healthy controls, patients with new onset type 1 diabetes, relatives participating to the TrialNet Pathway to Prevention who were, at blood collection, autoantibody negative or positive for a single autoantibody (low-risk individuals), and positive for multiple autoantibodies (high-risk individuals). Linear mixed models were adopted to estimate variation of pancreatic enzymes among the groups and to evaluate the influence of high-risk HLA genotypes and residual beta cell function on exocrine pancreas function. Results In adults, but not children, reduced levels of P-amylase and lipase were shown in at-risk individuals, including (for P-amylase levels only) those at low-risk, and in T1Dnew. Furthermore, while high-risk HLA genotypes negatively affected P-amylase levels in autoantibody negative adult individuals, fasting C-peptide levels did not correlate with pancreatic enzyme levels. Conclusions Exocrine pancreas dysfunction precedes the onset of type 1 diabetes in adult at-risk individuals and may be unrelated to fasting C-peptide levels.

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The Prediction of Type 1 Diabetes in discordant and concordant families: 16 years of follow-up. Focus on the future

Diabetes Mellitus ◽

10.14341/dm2014383-89 ◽

2014 ◽

Vol 17 (3) ◽

pp. 83-89

Author(s):

Elena Vital'evna Titovich ◽

Tamara Leonidovna Kuraeva ◽

Olga Nikolaevna Ivanova ◽

Svetlana Mikhailovna Stepanova ◽

Valentina Alexandrovna Peterkova ◽

...

Keyword(s):

Type 1 Diabetes ◽

High Risk ◽

Low Risk ◽

Research Centre ◽

Sick People ◽

Immunological Markers ◽

Forecasting Methods ◽

Hla Genotypes

For 40 years, research continues to improve the forecasting methods and the development of effective and safe methods of preventing type 1 diabetes mellitus (T1DM). Аim. Prediction of the early preclinical stage of T1DM. Materials and methods. We studied the predisposing and protective haplotypes (HLA-DRB1, gene DQ) together with immunological markers (ICA, GADA, IAA) in 224 discordant/concordant families. Results. At the Endocrinology Research Centre, population and family risks of the development of T1DM in Russia were calculated on the basis of population genetic approaches. The analysis of the prevalence of HLA genotypes among T1DM patients revealed that the high-risk haplotypes in the structure of genotype(s) DQ2 and/or DQ8 in combination with the others were 78%: of these genotypes DQ2/DQ8, DQ2/DQ2, and DQ8/DQ8 accounted for 35%; DQ2/X* and DQ8/X* accounted for 43%; and the low-risk genotype Х*/Х* accounted for 22%. The genotype Х/Х consisted of weaker predisposing haplotypes that were specific to the Russian population in combination with neutral haplotypes or those consisting of neutral haplotypes only. The analysis of patients with T1DM genotypes revealed that high-risk genotypes (DQ2/DQ8) were more common in ill children up to the age of 5 (33% of cases) than in T1DM children over 10 years (23%) (p=0.05). Conversely, the low-risk genotypes were significantly less likely to be found in children with manifestations of diabetes up to 5 years than in sick people over 10 years [5% and 13%, respectively (p

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1544-P: High Risk of Adverse Drug Reaction (ADR) in Older Adults with Type 1 Diabetes (T1D)

Diabetes ◽

10.2337/db19-1544-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1544-P ◽

Cited By ~ 3

Author(s):

ELENA TOSCHI ◽

CHRISTINE SLYNE ◽

ASTRID ATAKOV-CASTILLO ◽

KAYLA SIFRE ◽

ALYSSA B. DUFOUR ◽

...

Keyword(s):

Older Adults ◽

Adverse Drug Reaction ◽

Type 1 Diabetes ◽

Drug Reaction ◽

High Risk

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344-OR: Slowed Metabolic Decline after Oral Insulin (OI) in Relatives at High Risk for Type 1 Diabetes (T1D)

Diabetes ◽

10.2337/db20-344-or ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 344-OR

Author(s):

JAY SOSENKO ◽

JERRY P. PALMER ◽

MICHAEL J. HALLER ◽

JAY S. SKYLER ◽

ALBERTO PUGLIESE ◽

...

Keyword(s):

Type 1 Diabetes ◽

High Risk ◽

Oral Insulin

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Social Determinants of Health, Goals and Outcomes in High-Risk Children with Type 1 Diabetes

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2021.02.005 ◽

2021 ◽

Author(s):

J.A. Hershey ◽

J. Morone ◽

T.H. Lipman ◽

C.P. Hawkes

Keyword(s):

Type 1 Diabetes ◽

High Risk ◽

Social Determinants Of Health ◽

Social Determinants ◽

Determinants Of Health ◽

Health Goals ◽

High Risk Children

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Ultrasound evaluation of the fetal fat tissue, heart, liver and umbilical cord measurements in pregnancies complicated by gestational and type 1 diabetes mellitus: potential application in the fetal birth-weight estimation and prediction of the fetal macrosomia

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00634-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Paweł Jan Stanirowski ◽

Agata Majewska ◽

Michał Lipa ◽

Dorota Bomba-Opoń ◽

Mirosław Wielgoś

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Birth Weight ◽

Soft Tissue ◽

Type 1 Diabetes Mellitus ◽

Umbilical Cord ◽

Predictive Value ◽

Fetal Macrosomia ◽

Fetal Birth Weight

Abstract Background The aim of the study was to evaluate the ultrasound-derived measurements of the fetal soft-tissue, heart, liver and umbilical cord in pregnancies complicated by gestational (GDM) and type 1 diabetes mellitus (T1DM), and further to assess their applicability in the estimation of the fetal birth-weight and prediction of fetal macrosomia. Methods Measurements were obtained from diet-controlled GDM (GDMG1) (n = 40), insulin-controlled GDM (GDMG2) (n = 40), T1DM (n = 24) and healthy control (n = 40) patients. The following parameters were selected for analysis: fetal sub-scapular fat mass (SSFM), abdominal fat mass (AFM), mid-thigh fat/lean mass (MTFM/MTLM) and inter-ventricular septum (IVS) thicknesses, heart and thorax circumference and area (HeC/HeA; ThC/ThA), liver length (LL), umbilical cord/vein/arteries circumference and area (UmC/UmA; UvC/UvA; UaC/UaA) together with total umbilical vessels (UveA) and Wharton's jelly area (WjA). Regression models were created in order to assess the contribution of selected parameters to fetal birth-weight (FBW) and risk of fetal macrosomia. Results Measurements of the fetal SSFM, AFM, MTFM, MTFM/MTLM ratio, HeC, HeA, IVS, LL, UmC, UmA, UaC, UaA, UveA and WjA were significantly increased among patients with GDMG2/T1DM as compared to GDMG1 and/or control groups (p < .05). The regression analysis revealed that maternal height as well as fetal biparietal diameter, abdominal circumference (AC), AFM and LL measurements were independent predictors of the FBW (p < .05). In addition, increase in the fetal AFM, AC and femur length (FL) was associated with a significant risk of fetal macrosomia occurrence (p < .05). The equation developed for the FBW estimation [FBW(g) = − 2254,942 + 17,204 * FL (mm) + 105,531 * AC (cm) + 131,347 * AFM (mm)] provided significantly lower mean absolute percent error than standard formula in the sub-group of women with T1DM (5.7% vs 9.4%, p < .05). Moreover, new equation including AC, FL and AFM parameters yielded sensitivity of 93.8%, specificity 77.7%, positive predictive value 54.5% and negative predictive value of 97.8% in the prediction of fetal macrosomia. Conclusions Ultrasound measurements of the fetal soft tissue, heart, liver and umbilical cord are significantly increased among women with GDM treated with insulin and T1DM. In addition to standard biometric measurements, parameters, such as AFM, may find application in the management of diabetes-complicated pregnancies.

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Genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in Type 1 Diabetes from an admixed Brazilian population

Scientific Reports ◽

10.1038/s41598-021-93691-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rossana Santiago de Sousa Azulay ◽

Luís Cristóvão Porto ◽

Dayse Aparecida Silva ◽

Maria da Glória Tavares ◽

Roberta Maria Duailibe Ferreira Reis ◽

...

Keyword(s):

Type 1 Diabetes ◽

Native American ◽

Y Chromosome ◽

Chromosome Analysis ◽

Brazilian Population ◽

Genetic Ancestry ◽

Sample Sizes ◽

Chromosome Markers ◽

Hla Genotypes

AbstractThis study aimed to investigate the relationship between genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in patients with Type 1 Diabetes from an admixed Brazilian population. Inference of autosomal ancestry; HLA-DRB1, -DQA1 and -DQB1 typifications; and Y chromosome analysis were performed. European autosomal ancestry was about 50%, followed by approximately 25% of African and Native American. The European Y chromosome was predominant. The HLA-DRB1*03 and DRB1*04 alleles presented risk association with T1D. When the Y chromosome was European, DRB1*03 and DRB1*04 homozygote and DRB1*03/DRB1*04 heterozygote genotypes were the most frequent. The results suggest that individuals from Maranhão have a European origin as their major component; and are patrilineal with greater frequency from the R1b haplogroup. The predominance of the HLA-DRB1*03 and DRB1*04 alleles conferring greater risk in our population and being more frequently related to the ancestry of the European Y chromosome suggests that in our population, the risk of T1D can be transmitted by European ancestors of our process miscegenation. However, the Y sample sizes of Africans and Native Americans were small, and further research should be conducted with large mixed sample sizes to clarify this possible association.

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