| 1. |
- Ahrén, Bo
(författare)
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Glucose-dependent insulinotropic polypeptide secretion after oral macronutrient ingestion : The human literature revisited and a systematic study in model experiments in mice
- 2022
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116 .- 2040-1124. ; 13:10, s. 1655-1665
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Tidskriftsartikel (refereegranskat)abstract
- Aims/Introduction: The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is secreted after meal ingestion. This study explored the relative influence of classes of macronutrients on GIP secretion. Materials and Methods: The human literature was revisited by identifying articles from PubMed using key words GIP, macronutrients, carbohydrates, fat, protein, healthy subjects. In model experiments in anesthetized mice, glucose (25–125 mg), protein (15–120 mg), fat emulsion (6–100 mg) or saline was given orally with determination of GIP levels. Results: The literature survey identified 15 studies in which glucose, protein or fat was administered to healthy subjects. All three classes of macronutrients stimulated GIP secretion with a 30–45 min peak after glucose and protein, and a more prolonged release after fat. Limitations in study designs preclude firm conclusions on the relative potency of the macronutrients. In mice, glucose was more potent to stimulate GIP secretion than fat and protein, with no significant difference between protein and fat. By co-administration of the macronutrients at moderate caloric combinations, a synergistic stimulation of GIP secretion was observed. In contrast, when raising the glucose challenge together with protein and fat, no synergy, but an additive effect, was evident. Conclusions: Glucose, protein and fat all stimulate GIP secretion in humans and mice. In mice, glucose is more potent than fat and protein, and there is also a synergy between the macronutrients on GIP secretion at moderate caloric doses. Further studies are warranted in humans to explore the relative potency of macronutrients.
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| 2. |
- Ahrén, Bo, et al.
(författare)
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Glucose effectiveness : Lessons from studies on insulin-independent glucose clearance in mice
- 2021
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116 .- 2040-1124. ; 12:5, s. 675-685
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Forskningsöversikt (refereegranskat)abstract
- Besides insulin-mediated transport of glucose into the cells, an important role is also played by the non-insulin-mediated transport. This latter process is called glucose effectiveness (acronym SG), which is estimated by modeling of glucose and insulin data after an intravenous glucose administration, and accounts for ≈70% of glucose disposal. This review summarizes studies on SG, mainly in humans and rodents with focus on results achieved in model experiments in mice. In humans, SG is reduced in type 2 diabetes, in obesity, in liver cirrhosis and in some elderly populations. In model experiments in mice, SG is independent from glucose levels, but increases when insulin secretion is stimulated, such as after administration of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. SG is reduced in insulin resistance induced by high-fat feeding and by exogenous administration of glucagon. Glucose-dependent (insulin-independent) glucose disposal is therefore important for glucose elimination, and it is also well regulated. It might be of pathophysiological relevance for the development of type 2 diabetes, in particular during insulin resistance, and might also be a target for glucose-reducing therapy. Measuring SG is essentially important when carrying out metabolic studies to understand glucose homeostasis.
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| 3. |
- Ahrén, Bo
(författare)
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Glucose-lowering action through targeting islet dysfunction in type 2 diabetes : Focus on dipeptidyl peptidase-4 inhibition
- 2021
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116 .- 2040-1124. ; 12:7, s. 1128-1135
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Forskningsöversikt (refereegranskat)abstract
- Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP-4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium–glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP-4 is efficient in these populations. This mini-review highlights the islet mechanisms of DPP-4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP-4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin.
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| 4. |
- Chatterjee, Tulika, et al.
(författare)
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Type 1 diabetes, COVID-19 vaccines and short-term safety : Subgroup analysis from the global COVAD study
- 2024
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Ingår i: Journal of Diabetes Investigation. - : John Wiley & Sons. - 2040-1116 .- 2040-1124. ; 15:1, s. 131-138
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short-term (<7-day) adverse vaccination events (AEs) and their risk factors among type 1 diabetes patients. MATERIALS AND METHODS: This study analyzed data from the COVID-19 vaccination in Autoimmune Diseases (COVAD) survey database (May to December 2021; 110 collaborators, 94 countries), comparing <7-day COVID-19 vaccine AE among type 1 diabetes patients and healthy controls (HCs). Descriptive statistics; propensity score matching (1:4) using the variables age, sex and ethnicity; and multivariate analyses were carried out.RESULTS: This study analyzed 5,480 completed survey responses. Of all responses, 5,408 were HCs, 72 were type 1 diabetes patients (43 females, 48.0% white European ancestry) and Pfizer was the most administered vaccine (39%). A total of 4,052 (73.9%) respondents had received two vaccine doses. Patients with type 1 diabetes had a comparable risk of injection site pain, minor and major vaccine AEs, as well as associated hospitalizations to HCs. However, type 1 diabetes patients had a higher risk of severe rashes (3% vs 0.4%, OR 8.0, 95% confidence interval 1.7-36), P = 0.007), although reassuringly, these were rare (n = 2 among type 1 diabetes patients).CONCLUSIONS: COVID-19 vaccination was safe and well tolerated in patients with type 1 diabetes with similar AE profiles compared with HCs, although severe rashes were more common in type 1 diabetes patients.
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| 5. |
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| 6. |
- Liang, Hua, et al.
(författare)
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Recognition of maturity-onset diabetes of the young in China
- 2021
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116 .- 2040-1124. ; 12:4, s. 501-509
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Tidskriftsartikel (refereegranskat)abstract
- Aims/Introduction: Given that mutations related to maturity-onset diabetes of the young (MODY) are rarely found in Chinese populations, we aim to characterize the mutation spectrum of MODY pedigrees. Materials and Methods: Maturity-onset diabetes of the young candidate gene- or exome-targeted capture sequencing was carried out in 76 probands from unrelated families fulfilling the clinical diagnostic criteria for MODY. MAF <0.01 in the GnomAD or ExAC database was used to filter significant variants. Sanger sequencing was then carried out to validate findings. Function prediction by SIFT, PolyPhen-2 and PROVEAN or CADD was carried out in missense mutations. Results: A total of 32 mutations in six genes were identified in 31 families, accounting for 40.79% of the potential MODY families. The MODY subtype detection rate was 18.42% for GCK, 15.79% for HNF1A, 2.63% for HNF4A, and 1.32% for KLF11, PAX4 and NEUROG3. Seven nonsense/frameshift mutations and four missense mutations with damaging prediction were newly identified novel mutations. The clinical features of MODY2, MODY3/1 and MODYX are similar to previous reports. Clinical phenotype of NEUROG3 p.Arg55Glufs*23 is characterized by hyperglycemia and mild intermittent abdominal pain. Conclusions: This study adds to the emerging pattern of MODY epidemiology that the proportion of MODY explained by known pathogenic genes is higher than that previously reported, and found NEUROG3 as a new causative gene for MODY.
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| 7. |
- Wang, Zhida, et al.
(författare)
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Association between diabetes or antidiabetic therapy and lung cancer : A meta-analysis
- 2013
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Ingår i: Journal of Diabetes Investigation. - : Wiley-Blackwell. - 2040-1116 .- 2040-1124. ; 4:6, s. 659-666
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Tidskriftsartikel (refereegranskat)abstract
- Aims/IntroductionDiabetes can increase the risk of cancers at several sites, but the association between diabetes and lung cancer remains unclear. We aimed to provide the quantitative estimates for the association between diabetes or antidiabetic treatment and lung cancer risk in the present meta-analysis. Materials and MethodsCohort studies were identified by searching the PubMed database (January 1960 through October 2012) and manually assessing the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. ResultsA total of 19 cohort studies were included in the present meta-analysis. Of these, 14 studies focused on the association between diabetes and lung cancer incidence, and seven studies focused on the association between antidiabetic treatment and lung cancer incidence. Compared with non-diabetic individuals, diabetic patients do not have an increased risk of lung cancer (RR=1.04, 95% CI 0.87-1.24). The association between diabetes and lung cancer remained not statistically significant in subgroup analysis stratified by study characteristics, study quality, diabetes ascertainment or important confounders. A null association between insulin or biguanides therapy and lung cancer risk was found. However, the diabetic patients receiving thiazolidinedione (TZD) treatment had a 20% reduced risk of lung cancer than those without TZD treatment. ConclusionsNo association between diabetes and lung cancer risk was found. However, TZD treatment might reduce lung cancer risk in diabetic patients.
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| 8. |
- Yu, Yang, et al.
(författare)
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Apolipoprotein M overexpression through adeno-associated virus gene transfer improves insulin secretion and insulin sensitivity in Goto-Kakizaki rats
- 2020
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116 .- 2040-1124. ; 11:5, s. 1150-1158
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Tidskriftsartikel (refereegranskat)abstract
- Aims/Objective: The development of type 2 diabetes is a result of insulin resistance in various tissues, including skeletal muscle and liver. Apolipoprotein M (ApoM) plays an important role in the function of high-density lipoprotein, and also affects hepatic lipid and glucose metabolism. In this study, we aimed to investigate whether ApoM overexpression modulates glucose metabolism and improves insulin sensitivity. Materials and Methods: The Goto-Kakizaki (GK) rats were transfected with adeno-associated virus (AAV) encoding rat ApoM gene or control blank. The oral glucose tolerance test (OGTT) and hyperinsulinemic-euglycemic clamp (HEC) experiment were used to assess the insulin sensitivity of GK rats. Results: The results show that ApoM messenger ribonucleic acid and protein were significantly overexpressed in the pancreatic tissues. Overexpression of ApoM decreased fasting blood glucose and random blood glucose, improved glucose tolerance, and increased bodyweight and insulin levels in GK rats. The glucose infusion rate of rats in the AAV encoding rat ApoM gene group during HEC test was 1.04-, 1.23- and 1.95-fold higher than that in the AAV control blank group at 1–3 weeks after injection of AAV, respectively. A Wes-ProteinSimple assay and quantification was carried out to assess phosphorylated protein kinase B/protein kinase B protein levels in the muscle tissues of ApoM-overexpressing GK rats, and they were found to be higher than those of the control group at the seventh week after AAV injection. Conclusions: ApoM overexpression through adeno-associated virus gene transfer might improve insulin secretion and insulin sensitivity in GK rats.
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| 9. |
- Ahrén, Bo
(författare)
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DPP-4 inhibition and islet function
- 2012
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116. ; 3:1, s. 3-10
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Forskningsöversikt (refereegranskat)abstract
- During recent years, dipeptidyl peptidase-4 (DPP-4) inhibition has been included in the clinical management of type 2 diabetes, both as monotherapy and as add-on to several other therapies. DPP-4 inhibition prevents the inactivation of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). This results in stimulation of insulin secretion and inhibition of glucagon secretion, and there is also a potential beta-cell preservation effect, as judged from rodent studies; that is, it might target the key islet dysfunction in the disease. In type 2 diabetes. This reduces 24-h glucose levels and reduces HbA1c by approximate to 0.81.1% from baseline levels of 7.78.5%. DPP-4 inhibition is safe, with a very low risk for adverse events including hypoglycemia, and it prevents weight gain. The present review summarizes the studies on the influence of DPP-4 inhibition on islet function. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00184.x, 2012)
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| 10. |
- Ahrén, Bo
(författare)
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Glucagon-like peptide-1 receptor agonists for type 2 diabetes : A rational drug development
- 2019
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116. ; 10:2, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- Today, glucagon-like peptide-1 (GLP-1) receptor agonists are established glucose-lowering drugs used in the management of type 2 diabetes. Their development emerged from the understanding that a combined islet dysfunction comprising of impaired insulin secretion and exaggerated glucagon secretion is the key defect of hyperglycemia. GLP-1 was shown to target these defects, and after the discovery that dipeptidyl peptidase-4 inactivates native GLP-1, several different dipeptidyl peptidase-4-resistant GLP-1 receptor agonists have been developed. They are administered subcutaneously, but show differences in molecular structure, molecular size and pharmacokinetics, the latter allowing twice-daily, once-daily or once-weekly administration. They have been shown to be efficient in reducing both glycated hemoglobin and bodyweight, and to be safe and highly tolerable. Cardiovascular outcomes trials have shown them to be neutral or beneficial. GLP-1 receptor agonists are positioned as add-ons to metformin alone or in combination with oral agents in the clinical paradigm. They are also efficient when combined with insulin, and fixed dose combinations with long-acting insulin have been developed. Recent development includes a very long administration schedule and oral availability. The research from the first demonstration of the antidiabetic action of GLP-1 in the early 1990s to the enormously accumulated data today represents a successful and rational development, which has been characterized by focused perseverance to establish this therapy in the management of type 2 diabetes.
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