| 1. |
- Arora, G. P., et al.
(författare)
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Insulin secretion and action in North Indian women during pregnancy
- 2017
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Ingår i: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; 34:10, s. 1477-1482
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999) and adapted WHO 2013 (GDM2013) criteria, excluding the 1-h glucose value, in a high-risk Indian population from Punjab.METHODS: Insulin secretion (HOMA2-B) and insulin action (HOMA2-IR) were assessed in 4665 Indian women with or without gestational diabetes defined by the GDM1999 or adapted GDM2013 criteria.RESULTS: Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women with normal glucose tolerance, and furthermore displayed lower insulin secretion than GDM1999 women. Urban habitat, illiteracy, high age and low BMI were independently associated with reduced insulin secretion, whereas Sikh religion, increasing age and BMI, as well as a family history of diabetes were independently associated with increased insulin resistance.CONCLUSIONS: Gestational diabetes risk factors influence insulin secretion and action in North Indian women in a differential manner. Gestational diabetes classified using the adapted GDM2013 compared with GDM1999 criteria is associated with more severe impairments of insulin secretion and action.
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| 2. |
- Wibaek, Rasmus, et al.
(författare)
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Low birthweight is associated with a higher incidence of type 2 diabetes over two decades independent of adult BMI and genetic predisposition
- 2023
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Ingår i: Diabetologia. - 0012-186X. ; 66:9, s. 1669-1679
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes. Most previous studies are based on cross-sectional prevalence data, not designed to study the timing of onset of type 2 diabetes in relation to birthweight. We aimed to examine associations of birthweight with age-specific incidence rate of type 2 diabetes in middle-aged to older adults over two decades. Methods: Adults aged 30–60 years enrolled in the Danish Inter99 cohort in 1999–2001 (baseline examination), with information on birthweight from original birth records from 1939–1971 and without diabetes at baseline, were eligible. Birth records were linked with individual-level data on age at diabetes diagnosis and key covariates. Incidence rates of type 2 diabetes as a function of age, sex and birthweight were modelled using Poisson regression, adjusting for prematurity status at birth, parity, polygenic scores for birthweight and type 2 diabetes, maternal and paternal diabetes history, socioeconomic status and adult BMI. Results: In 4590 participants there were 492 incident type 2 diabetes cases during a mean follow-up of 19 years. Type 2 diabetes incidence rate increased with age, was higher in male participants, and decreased with increasing birthweight (incidence rate ratio [95% CI per 1 kg increase in birthweight] 0.60 [0.48, 0.75]). The inverse association of birthweight with type 2 diabetes incidence was statistically significant across all models and in sensitivity analysis. Conclusions/interpretation: A lower birthweight was associated with increased risk of developing type 2 diabetes independent of adult BMI and genetic risk of type 2 diabetes and birthweight. Graphical Abstract: [Figure not available: see fulltext.]
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| 3. |
- Arora, Geeti P, et al.
(författare)
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Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 286:2, s. 192-206
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population-based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia.METHODS: 85 GDM/T2D loci in European and/or Indian populations from previous studies were assessed for association with GDM based on Swedish GDM criteria in 4018 Punjabi Indian and 507 Swedish pregnant women. Selected loci were replicated in Scandinavian cohorts, Radiel (N=398, Finnish), STORK/STORK-G (N=780, Norwegian).RESULTS: Punjabi Indian women had higher GDM prevalence, lower insulin secretion and better insulin sensitivity than Swedish women. There were significant frequency differences of GDM/T2D risk alleles between both populations. rs7178572 at HMG20A, previously associated with GDM in South Indian and European women was replicated in North Indian women. The T2D risk SNP rs11605924 in the CRY2 gene was associated with increased GDM risk in Scandinavian but decreased risk in Punjabi Indian women. No other overlap was seen between GDM loci in both populations.CONCLUSIONS: GDM is more common in Indian than Swedish women, which partially can be attributed to differences in insulin secretion and action. There was marked heterogeneity in the GDM phenotypes between the populations which could only partially be explained by genetic differences. This article is protected by copyright. All rights reserved.
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| 4. |
- Domazet, Sidsel L., et al.
(författare)
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Low-grade inflammation in persons with recently diagnosed type 2 diabetes : The role of abdominal adiposity and putative mediators
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Ingår i: Diabetes, Obesity and Metabolism. - 1462-8902.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. Materials and Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. Results: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%–25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%–7%) and high triglyceride levels (2%–6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%–2%). Conclusions: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%–40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.
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| 5. |
- Elingaard-Larsen, Line O., et al.
(författare)
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Circulating Metabolomic and Lipidomic Signatures Identify a Type 2 Diabetes Risk Profile in Low-Birth-Weight Men with Non-Alcoholic Fatty Liver Disease
- 2023
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls (p ≤ 0.05), subgroup analyses of the LBW men with and without NAFLD revealed more pronounced differences, with 11 metabolites and 56 lipids differentiating (p ≤ 0.05) the groups. The differences in the LBW men with NAFLD included increased levels of ornithine and tyrosine (PFDR ≤ 0.1), as well as of triglycerides and phosphatidylcholines with shorter carbon-chain lengths and fewer double bonds. Pathway and network analyses demonstrated downregulation of transfer RNA (tRNA) charging, altered urea cycling, insulin resistance, and an increased risk of T2D in the LBW men with NAFLD. Our findings highlight the importance of increased liver fat in the pathogenesis of T2D in LBW individuals.
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| 6. |
- Hansen, Aleksander L., et al.
(författare)
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Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes
- 2023
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Ingår i: Diabetologia. - 0012-186X. ; 66:9, s. 1680-1692
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes but it is unknown whether low birthweight is associated with distinct clinical characteristics at disease onset. We examined whether a lower or higher birthweight in type 2 diabetes is associated with clinically relevant characteristics at disease onset. Methods: Midwife records were traced for 6866 individuals with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Using a cross-sectional design, we assessed age at diagnosis, anthropomorphic measures, comorbidities, medications, metabolic variables and family history of type 2 diabetes in individuals with the lowest 25% of birthweight (<3000 g) and highest 25% of birthweight (>3700 g), compared with a birthweight of 3000–3700 g as reference, using log-binomial and Poisson regression. Continuous relationships across the entire birthweight spectrum were assessed with linear and restricted cubic spline regression. Weighted polygenic scores (PS) for type 2 diabetes and birthweight were calculated to assess the impact of genetic predispositions. Results: Each 1000 g decrease in birthweight was associated with a 3.3 year (95% CI 2.9, 3.8) younger age of diabetes onset, 1.5 kg/m2 (95% CI 1.2, 1.7) lower BMI and 3.9 cm (95% CI 3.3, 4.5) smaller waist circumference. Compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity (prevalence ratio [PR] for Charlson Comorbidity Index Score ≥3 was 1.36 [95% CI 1.07, 1.73]), having a systolic BP ≥155 mmHg (PR 1.26 [95% CI 0.99, 1.59]), lower prevalence of diabetes-associated neurological disease, less likelihood of family history of type 2 diabetes, use of three or more glucose-lowering drugs (PR 1.33 [95% CI 1.06, 1.65]) and use of three or more antihypertensive drugs (PR 1.09 [95% CI 0.99, 1.20]). Clinically defined low birthweight (<2500 g) yielded stronger associations. Most associations between birthweight and clinical characteristics appeared linear, and a higher birthweight was associated with characteristics mirroring lower birthweight in opposite directions. Results were robust to adjustments for PS representing weighted genetic predisposition for type 2 diabetes and birthweight. Conclusion/interpretation: Despite younger age at diagnosis, and fewer individuals with obesity and family history of type 2 diabetes, a birthweight <3000 g was associated with more comorbidities, including a higher systolic BP, as well as with greater use of glucose-lowering and antihypertensive medications, in individuals with recently diagnosed type 2 diabetes.
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| 7. |
- Hjort, Line, et al.
(författare)
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36 h fasting of young men influences adipose tissue DNA methylation of LEP and ADIPOQ in a birth weight-dependent manner
- 2017
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short-term fasting on leptin (LEP) and adiponectin (ADIPOQ) DNA methylation and gene expression in subcutaneous adipose tissue (SAT) from subjects with LBW and NBW. Methods: Twenty-one young LBW men and 18 matched NBW controls were studied during 36 h fasting. Eight subjects from each group completed a control study (overnight fast). We analyzed SAT LEP and ADIPOQ methylation (Epityper MassARRAY), gene expression (q-PCR), and adipokine plasma levels. Results: After overnight fast (control study), LEP and ADIPOQ DNA methylation levels were higher in LBW compared to those in NBW subjects (p ≤ 0.03) and increased with 36 h fasting in NBW subjects only (p ≤ 0.06). Both LEP and ADIPOQ methylation levels were positively associated with total body fat percentage (p ≤ 0.05). Plasma leptin levels were higher in LBW versus NBW subjects after overnight fasting (p = 0.04) and decreased more than threefold in both groups after 36 h fasting (p ≤ 0.0001). Conclusions: This is the first study to demonstrate that fasting induces changes in DNA methylation. This was shown in LEP and ADIPOQ promoters in SAT among NBW but not LBW subjects. The altered epigenetic flexibility in LBW subjects might contribute to their differential response to fasting, adipokine levels, and increased risk of metabolic disease.
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| 8. |
- Rönn, Tina, et al.
(författare)
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Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:13, s. 3792-3813
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Tidskriftsartikel (refereegranskat)abstract
- Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed DNA methylation of ∼480,000 sites in human adipose tissue from 96 males and 94 females, and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1,050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of ageing in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2,825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with methylation of 711 sites, annotated to e.g. RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for metabolic diseases and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.
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