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| 2. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Metabolite profiling of LADA challenges the view of a metabolically distinct subtype
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:4, s. 806-814
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Tidskriftsartikel (refereegranskat)abstract
- Latent autoimmune diabetes in adults (LADA) usually refers to GAD65 autoantibodies (GADAb)-positive diabetes with onset after 35 years of age and no insulin treatment within the first 6 months after diagnosis. However, it is not always easy to distinguish LADA fromtype 1 or type 2 diabetes. In this study, we examined whether metabolite profiling could help to distinguish LADA (n = 50) from type 1 diabetes (n = 50) and type 2 diabetes (n = 50). Of 123 identified metabolites, 99 differed between the diabetes types. However, no unique metabolite profile could be identified for any of the types. Instead, the metabolome varied along a C-peptide-driven continuum from type 1 diabetes via LADA to type 2 diabetes. LADA was more similar to type 2 diabetes than to type 1 diabetes. In a principal component analysis, LADA patients overlapping with type 1 diabetes progressed faster to insulin therapy than those overlapping with type 2 diabetes. In conclusion, we could not find any unique metabolite profile distinguishing LADA from type 1 and type 2 diabetes. Rather, LADA was metabolically an intermediate of type 1 and type 2 diabetes, with those patients closer to the former showing a faster progression to insulin therapy than those closer to the latter.
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| 3. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Metabolite profiling paradoxically reveals favorable levels of lipids, markers of oxidative stress and unsaturated fatty acids in a diabetes susceptible group of Middle Eastern immigrants
- 2020
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 57:5, s. 597-603
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The population of immigrants from the Middle East in Sweden show a higher prevalence of type 2 diabetes (T2D) compared to native Swedes. The exact reason for this is unknown. Here, we have performed metabolite profiling to investigate these differences. Methods: Metabolite profiling was conducted in Iraqi immigrants (n = 93) and native Swedes (n = 77) using two complementary mass spectrometry-based platforms. Differences in metabolite levels were compared after adjustment for confounding anthropometric, diet and clinical variables. Results: The Iraqi immigrant population were more obese (44.1 vs 24.7%, p < 0.05), but had a lower prevalence of hypertension (32.3 vs 54.8%, p < 0.01) than the native Swedish population. We detected 140 metabolites, 26 of which showed different levels between populations (q < 0.05,) after adjustment for age, sex, BMI, T2D and use of metformin. Twenty-two metabolites remained significant after further adjustment for HOMA-IR, HOMA-beta or insulin sensitivity index. Levels of polyunsaturated acylcarnitines (14:2 and 18:2) and fatty acid (18:2) were higher, whereas those of saturated and monounsaturated acylcarnitines (14:0, 18:1, and 8:1), fatty acids (12:0, 14:0, 16:0, and 18:1), uremic solutes (urate and quinate) and ketone bodies (beta-hydroxybutyrate) were lower in Iraqi immigrants. Further, levels of phospholipids were generally lower in the Iraqi immigrant population. Conclusions: Our result suggests an overall beneficial lipid profile in Iraqi immigrants, despite a higher risk to develop T2D. Higher levels of polyunsaturated fatty acids may suggest differences in dietary pattern, which in turn may reduce the risk of hypertension.
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| 4. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Population-level analysis to determine parameters that drive variation in the plasma metabolite profiles
- 2018
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of flight mass spectrometry (QTOF-MS) to determine 106 metabolites in plasma samples from 2503 subjects in a cross-sectional study. We investigated the correlation structure of the metabolite profiles and generated uncorrelated metabolite factors using principal component analysis (PCA) and varimax rotation. Finally, we investigated associations between these factors and 34 clinical covariates. Our results suggest that liver function, followed by kidney function and insulin resistance show the strongest associations with the plasma metabolite profile. The association of specific phenotypes with several components may suggest multiple independent metabolic mechanisms, which is further supported by the composition of the associated factors. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
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| 5. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Treatment of Swedish Patients with Graves' Hyperthyroidism Is Associated with Changes in Acylcarnitine Levels
- 2017
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert Inc. - 1557-9077. ; 27:9, s. 1109-1117
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hyperthyroidism is associated with alterations in metabolism that are currently only partially understood. The objective of the study was to investigate changes in metabolism associated with reinstatement of euthyroidism in Swedish patients.METHODS: Eighty metabolites in plasma were profiled from 10 subjects with Graves' disease (GD) at baseline and after 9 and 15 months of treatment to reinstate euthyroidism. Thyroid parameters, thyrotropin (TSH), TSH receptor antibodies, free triiodothyronine, and free thyroxine were followed. Main findings were validated in plasma from 20 subjects with GD at baseline and at three, six, and nine months. The study was conducted at the endocrinology clinic in Malmö, Sweden.RESULTS: Euthyroidism was reinstated at three months, and thyroid status did not change further during the 15-month follow-up. This was paralleled by altered levels of 9/19 detected acylcarnitines (p < 0.05 after adjustment for multiple testing). Levels of short-chain acylcarnitines were decreased, intermediate-chain acylcarnitines elevated, and long-chain acylcarnitines unaltered.CONCLUSIONS: GD and treatment of the disease is associated with pronounced acyl chain length-dependent alterations in acylcarnitine levels. These changes may be impacted by ethnicity and or dietary differences.
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| 6. |
- Andersson, Lotta E., et al.
(författare)
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Glutamine-elicited secretion of glucagon-like peptide 1 is governed by an activated glutamate dehydrogenase
- 2018
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:3, s. 372-384
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide 1 (GLP-1), secreted from intestinal L cells, glucose dependently stimulates insulin secretion from β-cells. This glucose dependence prevents hypoglycemia, rendering GLP-1 analogs a useful and safe treatment modality in type 2 diabetes. Although the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear. We investigated how GLP-1 secretion is metabolically coupled in L cells (GLUTag) and in vivo inmice using the insulin-secreting cell line INS-1 832/13 as reference. A membrane-permeable glutamate analog (dimethylglutamate [DMG]), acting downstream of electrogenic transporters, elicited similar alterations in metabolism as glutamine in both cell lines. Both DMG and glutamine alone elicited GLP-1 secretion in GLUTag cells and in vivo, whereas activation of glutamate dehydrogenase (GDH) was required to stimulate insulin secretion from INS-1 832/13 cells. Pharmacological inhibition in vivo of GDH blocked secretion of GLP-1 in response to DMG. In conclusion, our results suggest that nonelectrogenic nutrient uptake and metabolism play an important role in L cell stimulus-secretion coupling. Metabolism of glutamine and related analogs by GDH in the L cell may explain why GLP-1 secretion, but not that of insulin, is activated by these secretagogues in vivo.
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| 7. |
- Andersson, Lotta E., et al.
(författare)
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Glycogen metabolism in the glucose-sensing and supply-driven β-cell
- 2016
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793. ; 590:23, s. 4242-4251
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Tidskriftsartikel (refereegranskat)abstract
- Glycogen metabolism in β-cells may affect downstream metabolic pathways controlling insulin release. We examined glycogen metabolism in human islets and in the rodent-derived INS-1 832/13 β-cells and found them to express the same isoforms of key enzymes required for glycogen metabolism. Our findings indicate that glycogenesis is insulin-independent but influenced by extracellular glucose concentrations. Levels of glycogen synthase decrease with increasing glucose concentrations, paralleling accumulation of glycogen. We did not find cAMP-elicited glycogenolysis and insulin secretion to be causally related. In conclusion, our results reveal regulated glycogen metabolism in human islets and insulin-secreting cells. Whether glycogen metabolism affects insulin secretion under physiological conditions remains to be determined.
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| 8. |
- Balderas Arroyo, Claudia, et al.
(författare)
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A randomized trial involving a multifunctional diet reveals systematic lipid remodeling and improvements in cardiometabolic risk factors in middle aged to aged adults
- 2023
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Ingår i: Frontiers in Nutrition. - 2296-861X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A multifunctional diet (MFD) combining foods and ingredients with proven functional properties, such as fatty fish and fiber-rich foods, among others, was developed and shown to markedly reduce cardiometabolic risk-associated factors.OBJECTIVE: Here, we aim at examining metabolic physiological changes associated with these improvements.METHODS: Adult overweight individuals without other risk factors were enrolled in an 8-week randomized controlled intervention following a parallel design, with one group ( n = 23) following MFD and one group ( n = 24) adhering to a control diet (CD) that followed the caloric formula (E%) advised by the Nordic Nutritional Recommendations. Plasma metabolites and lipids were profiled by gas chromatography and ultrahigh performance liquid chromatography/mass spectrometry. RESULTS: Weight loss was similar between groups. The MFD and CD resulted in altered levels of 137 and 78 metabolites, respectively. Out of these, 83 were uniquely altered by the MFD and only 24 by the CD. The MFD-elicited alterations in lipid levels depended on carbon number and degree of unsaturation.CONCLUSION: An MFD elicits weight loss-independent systematic lipid remodeling, promoting increased circulating levels of long and highly unsaturated lipids.CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02148653?term=NCT02148653&draw=2&rank=1, NCT02148653.
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| 9. |
- Herzog, Katharina, et al.
(författare)
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Metabolic Effects of Gastric Bypass Surgery : Is It All About Calories?
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 69:9, s. 2027-2035
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery is an efficient method to induce weight loss and also, frequently, remission of type 2 diabetes (T2D). Unpaired studies have shown bariatric surgery and dietary interventions to differentially affect multiple hormonal and metabolic parameters, suggesting that bariatric surgery causes T2D remission at least partially via unique mechanisms. In the current study, plasma metabolite profiling was conducted in patients with (n = 10) and without T2D (n = 9) subjected to Roux-en-Y gastric bypass surgery (RYGB). Mixed-meal tests were conducted at baseline, after the presurgical very-low-calorie diet (VLCD) intervention, immediately after RYGB, and after a 6-week recovery period. Thereby, we could compare fasted and postprandial metabolic consequences of RYGB and VLCD in the same patients. VLCD yielded a pronounced increase in fasting acylcarnitine levels, whereas RYGB, both immediately and after a recovery period, resulted in a smaller but opposite effect. Furthermore, we observed profound changes in lipid metabolism following VLCD but not in response to RYGB. Most changes previously associated with RYGB were found to be consequences of the presurgical dietary intervention. Overall, our results question previous findings of unique metabolic effects of RYGB and suggest that the effect of RYGB on the metabolite profile is mainly attributed to caloric restriction.
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| 10. |
- Jain, Ruchi, et al.
(författare)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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