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Age-related changes in lipid and glucose levels associated with drug use and mortality : an observational study
Rene Markovič, Vladimir Grubelnik, Helena Blažun Vošner, Peter Kokol, Matej Završnik, Karmen Janša, Marjeta Zupet, Jernej Završnik, Marko Marhl, 2022, original scientific article

Abstract: Background: The pathogenesis of type 2 diabetes mellitus is complex and still unclear in some details. The main feature of diabetes mellitus is high serum glucose, and the question arises of whether there are other statistically observable dysregulations in laboratory measurements before the state of hyperglycemia becomes severe. In the present study, we aim to examine glucose and lipid profiles in the context of age, sex, medication use, and mortality. Methods: We conducted an observational study by analyzing laboratory data from 506,083 anonymized laboratory tests from 63,606 different patients performed by a regional laboratory in Slovenia between 2008 and 2019. Laboratory data-based results were evaluated in the context of medication use and mortality. The medication use database contains anonymized records of 1,632,441 patients from 2013 to 2018, and mortality data were obtained for the entire Slovenian population. Results: We show that the highest percentage of the population with elevated glucose levels occurs approximately 20 years later than the highest percentage with lipid dysregulation. Remarkably, two distinct inflection points were observed in these laboratory results. The first inflection point occurs at ages 55 to 59 years, corresponding to the greatest increase in medication use, and the second coincides with the sharp increase in mortality at ages 75 to 79 years. Conclusions: Our results suggest that medications and mortality are important factors affecting population statistics and must be considered when studying metabolic disorders such as dyslipidemia and hyperglycemia using laboratory data.
Keywords: diabetes, metabolic syndrome, hematological data, aging
Published in DKUM: 21.05.2024; Views: 100; Downloads: 1
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Lipotoxicity in a vicious cycle of pancreatic beta cell exhaustion
Vladimir Grubelnik, Jan Zmazek, Matej Završnik, Marko Marhl, 2022, original scientific article

Abstract: Hyperlipidemia is a common metabolic disorder in modern society and may precede hyperglycemia and diabetes by several years. Exactly how disorders of lipid and glucose metabolism are related is still a mystery in many respects. We analyze the effects of hyperlipidemia, particularly free fatty acids, on pancreatic beta cells and insulin secretion. We have developed a computational model to quantitatively estimate the effects of specific metabolic pathways on insulin secretion and to assess the effects of short- and long-term exposure of beta cells to elevated concentrations of free fatty acids. We show that the major trigger for insulin secretion is the anaplerotic pathway via the phosphoenolpyruvate cycle, which is affected by free fatty acids via uncoupling protein 2 and proton leak and is particularly destructive in long-term chronic exposure to free fatty acids, leading to increased insulin secretion at low blood glucose and inadequate insulin secretion at high blood glucose. This results in beta cells remaining highly active in the “resting” state at low glucose and being unable to respond to anaplerotic signals at high pyruvate levels, as is the case with high blood glucose. The observed fatty-acid-induced disruption of anaplerotic pathways makes sense in the context of the physiological role of insulin as one of the major anabolic hormones.
Keywords: diabetes, insulin secretion, lipids, PEP cycle, uncoupling proteins, mitochondrial dysfunction
Published in DKUM: 20.05.2024; Views: 77; Downloads: 2
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