Nikoline Nygaard1 · Anne Kirstine Eriksen2 · Lars Ängquist3 · Daniel Belstrøm1 · Evelina Stankevic3 · Torben Hansen3 · Anja Olsen2 · Merete Markvart1
Received: 15 August 2024 / Accepted: 22 December 2024 / Published online: 13 January 2025 © The Author(s) 2025
Abstract
Background Evidence suggests a bidirectional relationship between oral health status and type 2 diabetes (T2D) in adults. Studies on associations between childhood oral health and T2D in adulthood are lacking.
Methods This is a nationwide Danish registry-based cohort study of individuals born between 1963 and 1972, having at least one registration in the National Child Odontology Registry between 1972 and 1987 (n=627,758). Follow-up lasted from 1995 to 2018. Main exposure variables were the highest achieved levels of dental caries and gingivitis between 1972 and 1987. The outcome was T2D diagnosis during follow-up. Data was analyzed using Cox-regression, stratified on sex, with age as the underlying timescale and highest achieved level of education between age 25–30 years as Cox-strata. Main analyses were conducted with and without age-restrictions (T2D diagnosis before/after age 40).
Results Compared to lowest-level references, high levels of gingivitis associated with increased hazard ratios (HRs) of T2D in both males (HR [95% confidence interval]: 1.59 [1.47; 1.72]) and females (1.87 [1.68; 2.08]), as did severe dental caries (males: (1.15 [1.04; 1.27], in females: 1.19 [1.06; 1.35]). Below age 40, gingivitis associated with increased HRs in males (1.84 ([1.58; 2.15]) and females (1.94 [1.63; 2.30]). Above age 40, both exposures displayed higher HRs in males (high gin-givitis: 1.52 [1.39; 1.66] vs. severe caries: 1.23 [1.09; 1.38]) and females (1.83 [1.59; 2.10] vs. 1.37 [1.17; 1.59]).
Conclusions Data suggest an association between childhood dental caries and gingivitis with risk of receiving a T2D diag-nosis in adulthood. However, results are affected by residual confounding warranting further studies.
Keywords Cohort studies · Dental caries · Diabetes mellitus · Type 2 · Gingivitis
Sunita M. C. De Sousa1,2,3 · Jennifer M. N. Phan4,5 · Amanda Wells4 · Kathy H. C. Wu6,7,8,9 · Hamish S. Scott1,4,10
Received: 12 December 2024 / Accepted: 3 January 2025 / Published online: 16 January 2025 © The Author(s) 2025, corrected publication 2025
Aims To assess the utility of reanalysing GCK variants of uncertain significance (VUS) as an intervention to improve the detection of monogenic diabetes.
Methods We examined GCK VUS in a local cohort of individuals with suspected monogenic diabetes and re-curated each variant against the recent ClinGen GCK-specific variant classification guidelines.
Results Variant reanalysis achieved a new ‘likely pathogenic’ classification (i.e., positive results) in 4/8 identified VUS.The single most common newly applied criterion indicating variant pathogenicity was a confirmed phenotype of GCK-hyperglycaemia. RNA sequencing and segregation studies were performed in two cases but not additive to reclassification.
Conclusions This is the first VUS reclassification study in monogenic diabetes using gene-specific guidelines. Within the limits of this small study, we observed a high rate (50%) of VUS upgrades to a positive result, thereby confirming the util-ity of VUS reanalysis– particularly with biochemical phenotyping– in increasing the detection of monogenic diabetes. We recommend HbA1c, fasting blood glucose and either pancreatic autoantibody negativity or a small oral glucose tolerance test increment as a feasible minimum dataset to inform variant classification at the individual patient level, noting the ongoing work of the ClinGen Monogenic Diabetes Expert Panel in systematically reviewing GCK variants at the international level.
Keywords Glucokinase · Monogenic diabetes · DNA sequencing · Genetics
Abbreviations
PVS Pathogenic very strong
PS Pathogenic strong
PM Pathogenic moderate
PP Pathogenic supporting
FHx Family history
AR Autosomal recessive
del/ins Deletion/insertion
IFG Impaired fasting glucose
OGTT Oral glucose tolerance test
Communicated by Massimo Federici, M.D.
Sunita M. C. De Sousa
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1 Adelaide Medical School, University of Adelaide, Adelaide, Australia
2 Endocrine & Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
3 Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, Australia
4 Department of Genetics & Molecular Pathology, SA Pathology, Adelaide, Australia
5 Flinders Medical School, Flinders University, Adelaide, Australia
6 Clinical Genomics, St Vincent’s Hospital, Darlinghurst, Australia
7 School of Medicine, University of New South Wales, Sydney, Australia
8 Discipline of Genomic Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
9 School of Medicine, University of Notre Dame, Sydney, Australia
10 Centre for Cancer Biology, an alliance between SA Pathology, University of South Australia, Adelaide, Australia
This article is excerpted from the 《Frontiers in Plant Science》 by Wound World
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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