| 1. |
- Færch, Kristine, et al.
(författare)
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Insulin resistance is accompanied by increased fasting glucagon and delayed glucagon suppression in individuals with normal and impaired glucose regulation
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:11, s. 3473-3481
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Tidskriftsartikel (refereegranskat)abstract
- Hyperinsulinemia is an adaptive mechanism that enables the maintenance of normoglycemia in the presence of insulin resistance. We assessed whether glucagon is also involved in the adaptation to insulin resistance. A total of 1,437 individuals underwent an oral glucose tolerance test with measurements of circulating glucose, insulin, and glucagon concentrations at 0, 30 and 120 min. Early glucagon suppression was defined as suppression in the period from 0 to 30 min, and late glucagon suppression as 30 to 120 min after glucose intake. Insulin sensitivity was estimated by the validated insulin sensitivity index. Individuals with screen-detected diabetes had 30% higher fasting glucagon levels and diminished early glucagon suppression, but greater late glucagon suppression when compared with individuals with normal glucose tolerance (P 0.014). Higher insulin resistance was associated with higher fasting glucagon levels, less early glucagon suppression, and greater late glucagon suppression (P < 0.001). The relationship between insulin sensitivity and fasting glucagon concentrations was nonlinear (P < 0.001). In conclusion, increased fasting glucagon levels and delayed glucagon suppression, together with increased circulating insulin levels, develop in parallel with insulin resistance. Therefore, glucose maintenance during insulin resistance may depend not only on hyperinsulinemia but also on the ability to suppress glucagon early after glucose intake.
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| 2. |
- Lundgaard, Agnete T., et al.
(författare)
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BALDR : A Web-based platform for informed comparison and prioritization of biomarker candidates for type 2 diabetes mellitus
- 2023
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Ingår i: PLoS Computational Biology. - 1553-734X. ; 19:8 August
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Tidskriftsartikel (refereegranskat)abstract
- Novel biomarkers are key to addressing the ongoing pandemic of type 2 diabetes mellitus. While new technologies have improved the potential of identifying such biomarkers, at the same time there is an increasing need for informed prioritization to ensure efficient downstream verification. We have built BALDR, an automated pipeline for biomarker comparison and prioritization in the context of diabetes. BALDR includes protein, gene, and disease data from major public repositories, text-mining data, and human and mouse experimental data from the IMI2 RHAPSODY consortium. These data are provided as easy-to-read figures and tables enabling direct comparison of up to 20 biomarker candidates for diabetes through the public website https://baldr.cpr.ku.dk.
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| 3. |
- Vistisen, Dorte, et al.
(författare)
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Bimodal distribution of glucose is not universally useful for diagnosing diabetes
- 2009
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 32:3, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Bimodality in the distribution of glucose has been used to define the cut point for the diagnosis of diabetes. Previous studies on bimodality have primarily been in populations with a high prevalence of type 2 diabetes, including one study in a white Caucasian population. All studies included participants with known diabetes. The aim of this study was to assess whether a bimodal structure is a general phenomenon in fasting plasma glucose (FPG) and 2-h plasma glucose that is useful for deriving a common cut point for diabetes in populations of different origin, both including and excluding known diabetes. RESEARCH DESIGN AND METHODS: The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project is an international collaboration pooling surveys from all continents. These studies include surveys in which plasma glucose was measured during an oral glucose tolerance test; in total, 43 studies (135,383 participants) from 27 countries were included. A mixture of two normal distributions was fitted to plasma glucose levels, and a cut point for normal glycemia was estimated as their intersection. In populations with a biologically meaningful cut point, bimodality was tested for significance. RESULTS: Distributions of FPG and 2-h plasma glucose did not, in general, produce bimodal structures useful for deriving cut points for diabetes. When present, the cut points produced were inconsistent over geographical regions. CONCLUSIONS: Deriving cut points for normal glycemia from distributions of FPG and 2-h plasma glucose does not appear to be suitable for defining diagnostic cut points for diabetes.
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| 4. |
- 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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| 5. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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