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  • 1
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    Online Resource
    Vitamin B12 and Folate Concentrations in Recent-onset Type 2 Diabetes and the Effect of Metformin Treatment
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 6 ( 2020-06-01), p. e2222-e2231
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 6 ( 2020-06-01), p. e2222-e2231
    Abstract: Vitamin B12 and folate deficiency are not only linked to hematological, neurological, and cardiovascular diseases, but are also associated with insulin resistance. Metformin can decrease vitamin B12 and folate concentrations. Objective To examine (1) effects of short-term metformin treatment on serum holotranscobalamin (holoTC) and folate and (2) their association with insulin sensitivity in recent-onset type 2 diabetes. Design This cross-sectional analysis comprised patients (known disease duration & lt;12 months) on metformin monotherapy (MET, n = 123, 81 males, 53 ± 12 years) or nonpharmacological treatment (NPT, n = 126, 77 males, 54 ± 11 years) of the German Diabetes Study. Main Outcome Measures HoloTC (enzyme-linked immunosorbent assay), cobalamin, and folate (electrochemiluminescence); beta-cell function and whole-body insulin sensitivity, measured during fasting (HOMA-B, HOMA-IR) and intravenous glucose tolerance tests combined with hyperinsulinemic–euglycemic clamp tests. Results HoloTC (105.4 [82.4, 128.3] vs 97 [79.7, 121.9] pmol/L) and folate concentrations (13.4 [9.3, 19.3] vs 12.7 [9.3, 22.0] nmol/L) were similar in both groups. Overall, holoTC was not associated with fasting or glucose-stimulated beta-cell function and insulin-stimulated glucose disposal. Cobalamin measurements yielded similar results in representative subgroups. In NPT but not MET, folate levels were inversely correlated with HOMA-IR (r = –0.239, P = .007). Folate levels did not relate to insulin sensitivity or insulin secretion in the whole cohort and in each group separately after adjustment for age, body mass index, and sex. Conclusions Metformin does not affect circulating holoTC and folate concentrations in recent-onset type 2 diabetes, rendering monitoring of vitamin B12 and folate dispensable, at least during the first 6 months after diagnosis or initiation of metformin.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa150
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 2
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    Hungry for your alanine: when liver depends on muscle proteolysis
    American Society for Clinical Investigation ; 2019
    In:  Journal of Clinical Investigation Vol. 129, No. 11 ( 2019-9-23), p. 4563-4566
    Details
    In: Journal of Clinical Investigation, American Society for Clinical Investigation, Vol. 129, No. 11 ( 2019-9-23), p. 4563-4566
    Type of Medium: Online Resource
    ISSN: 0021-9738 , 1558-8238
    URL: Article
    DOI: 10.1172/JCI131931
    Language: English
    Publisher: American Society for Clinical Investigation
    Publication Date: 2019
    detail.hit.zdb_id: 2018375-6
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  • 3
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    Metabolic surgery-induced changes of the growth hormone system relate to improved adipose tissue function
    Springer Science and Business Media LLC ; 2023
    In:  International Journal of Obesity Vol. 47, No. 6 ( 2023-06), p. 505-511
    Details
    In: International Journal of Obesity, Springer Science and Business Media LLC, Vol. 47, No. 6 ( 2023-06), p. 505-511
    Abstract: Body weight loss improves insulin resistance and growth hormone secretion in obesity, which may be regulated by leptin according to preclinical studies. How changes in leptin, lipids and insulin sensitivity after bariatric (metabolic) surgery affect the human growth hormone system is yet unclear. Participants and methods People with obesity (OBE, n  = 79, BMI 50.8 ± 6.3 kg/m 2 ) were studied before, 2, 12, 24 and 52 weeks after metabolic surgery and compared to lean healthy humans (control; CON, n  = 24, BMI 24.3 ± 3.1 kg/m 2 ). Tissue-specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps with D-[6,6- 2 H 2 ]glucose. Fasting leptin, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and IGF-binding proteins (IGFBP1, IGFBP3) were measured using ELISA. Results At baseline, OBE exhibited higher glycemia and leptinemia as well as pronounced peripheral, adipose tissue and hepatic insulin resistance compared to CON. GH and IGFBP1 were lower, while IGF1 was comparable between groups. At 52 weeks, OBE had lost 33% body weight and doubled their peripheral insulin sensitivity, which was paralleled by continuous increases in GH, IGF-1 and IGFBP1 as well as decrease in leptin. The rise in GH correlated with reductions in free fatty acids, adipose tissue insulin resistance and insulinemia, but not with changes in body weight, peripheral insulin sensitivity, glycemia or leptinemia. The rise in IGF-1 correlated with reduction in high-sensitive C-reactive protein. Conclusion Reversal of alterations of the GH-IGF-1 axis after surgically-induced weight loss is unlikely related to improved leptin secretion and/or insulin sensitivity, but is rather associated with restored adipose tissue function and reduced low-grade inflammation.
    Type of Medium: Online Resource
    ISSN: 0307-0565 , 1476-5497
    URL: Article
    DOI: 10.1038/s41366-023-01292-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2101927-7
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  • 4
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    1412-P: Preexisting Nonalcoholic Steatohepatitis Attenuates Improvement of Adipose Tissue OXPHOS Capacity after Weight-Loss Surgery
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Impaired adipose tissue (AT) function closely associates with obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) . Mitochondrial oxidative phosphorylation (OXPHOS) capacity of AT improves after weight loss surgery. However, it is not clear if the improvement is affected by the presence of NAFLD before surgery. We examined 52 severely obese people exhibiting no histological liver disease (OBE_CON) , simple steatosis (OBE_NAFL) or steatohepatitis (OBE_NASH) before (0 weeks) , 12 and 52 weeks after bariatric surgery. Whole-body insulin sensitivity was measured by hyperinsulinemic euglycemic clamps. OXPHOS capacity of subcutaneous AT was assessed by high-resolution respirometry. Transcript levels of TNFα in AT were quantified by RT-PCR. Before surgery, OBE_NASH presented with lower insulin sensitivity and higher HbA1c compared to OBE_CON and OBE_NAFL (all p & lt;0.05) whereas OXPHOS capacity in AT was comparable between the groups. Maximum coupled respiration declined at week 12 by 17% from week 0 in OBE_CON only (p & lt;0.05) . From 12 to 52 weeks, AT maximum coupled respiration markedly increased by 82 and 49% in OBE_CON and OBE_NAFL (both p & lt;0.001) but only by 28% in OBE_NASH (p=0.05; maximum coupled OXPHOS at week 52: OBE_CON vs. OBE_NASH p & lt;0.05) . The changes in AT maximum coupled respiration from 12 to 52 weeks correlated negatively with changes in AT TNFα levels in OBE_CON (β=-0.83, p & lt;0.001) and negatively with changes in systemic C-reactive protein levels in OBE_NASH (β=-0.34, p & lt;0.05) . Maximal noncoupled OXPHOS yielded similar changes and correlations. In conclusion, in severe obesity, weight loss-related improvements in AT OXPHOS capacity may be mediated to a great extent by reduced AT inflammation in people without liver disease; however, with pre-surgery manifestation of NASH and worsening of metabolic control, residual systemic subclinical inflammation may attenuate the improvement of AT OXPHOS capacity after bariatric surgery. Disclosure S.Kahl: None. G.Heilmann: None. I.Esposito: None. M.Schlensak: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. K.Strassburger: None. S.Gancheva: None. N.Saatmann: None. C.Granata: None. C.Herder: Research Support; Sanofi. K.Pafili: None. J.Puetzer-furmanczak: None. T.Sarabhai: None. Funding German Federal Ministry of Health; Ministry of Culture and Science of the State North Rhine-Westphalia;German Federal Ministry of Education and Research;European Funds for Regional Development (EFRE-0400191) ;EUREKA Eurostars-2 (E!113230DIA-PEP) ;German Science Foundation (CRC/SFB1116/2 B12; RTG/GRK 2576 vivid, Project 3) ;Schmutzler Stiftung
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-1412-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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  • 5
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    Comparison of 18F-FDG PET/MRI and MRI for pre-therapeutic tumor staging of patients with primary cancer of the uterine cervix
    Springer Science and Business Media LLC ; 2018
    In:  European Journal of Nuclear Medicine and Molecular Imaging Vol. 45, No. 1 ( 2018-1), p. 67-76
    Details
    In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 45, No. 1 ( 2018-1), p. 67-76
    Type of Medium: Online Resource
    ISSN: 1619-7070 , 1619-7089
    URL: Article
    DOI: 10.1007/s00259-017-3809-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2098375-X
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  • 6
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    High-intensity interval training for 12 weeks improves cardiovascular autonomic function but not somatosensory nerve function and structure in overweight men with type 2 diabetes
    Springer Science and Business Media LLC ; 2022
    In:  Diabetologia Vol. 65, No. 6 ( 2022-06), p. 1048-1057
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 65, No. 6 ( 2022-06), p. 1048-1057
    Abstract: It remains unclear whether and which modality of exercise training as a component of lifestyle intervention may exert favourable effects on somatosensory and autonomic nerve tests in people with type 2 diabetes. Methods Cardiovascular autonomic and somatosensory nerve function as well as intraepidermal nerve fibre density (IENFD) were assessed in overweight men with type 2 diabetes (type 2 diabetes, n  = 20) and male glucose-tolerant individuals (normal glucose tolerance [NGT], n  = 23), comparable in age and BMI and serving as a control group, before and after a supervised high-intensity interval training (HIIT) intervention programme over 12 weeks. Study endpoints included clinical scores, nerve conduction studies, quantitative sensory testing, IENFD, heart rate variability, postural change in systolic blood pressure and spontaneous baroreflex sensitivity (BRS). Results After 12 weeks of HIIT, resting heart rate decreased in both groups ([mean ± SD] baseline/12 weeks: NGT: 65.1 ± 8.2/60.2 ± 9.0 beats per min; type 2 diabetes: 68.8 ± 10.1/63.4 ± 7.8 beats per min), while three BRS indices increased (sequence analysis BRS: 8.82 ± 4.89/14.6 ± 11.7 ms 2 /mmHg; positive sequences BRS: 7.19 ± 5.43/15.4 ± 15.9 ms 2 /mmHg; negative sequences BRS: 12.8 ± 5.4/14.6 ± 8.7 ms 2 /mmHg) and postural change in systolic blood pressure decreased (−13.9 ± 11.6/−9.35 ± 9.76 mmHg) in participants with type 2 diabetes, and two heart rate variability indices increased in the NGT group (standard deviation of R–R intervals: 36.1 ± 11.8/55.3 ± 41.3 ms; coefficient of R–R interval variation: 3.84 ± 1.21/5.17 ± 3.28) (all p 〈 0.05). In contrast, BMI, clinical scores, nerve conduction studies, quantitative sensory testing, IENFD and the prevalence rates of diabetic sensorimotor polyneuropathy and cardiovascular autonomic neuropathy remained unchanged in both groups. In the entire cohort, correlations between the changes in two BRS indices and changes in $$ \dot{V}{\mathrm{O}}_{2\max } $$ V ̇ O 2 max over 12 weeks of HIIT (e.g. sequence analysis BRS: r  = 0.528, p =0.017) were observed. Conclusions/interpretation In male overweight individuals with type 2 diabetes, BRS, resting heart rate and orthostatic blood pressure regulation improved in the absence of weight loss after 12 weeks of supervised HIIT. Since no favourable effects on somatic nerve function and structure were observed, cardiovascular autonomic function appears to be more amenable to this short-term intervention, possibly due to improved cardiorespiratory fitness. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-022-05674-w
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458993-X
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  • 7
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    1212-P: Adipose Tissue Mitochondrial Function in Humans with Varying Liver Histology
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. Supplement_1 ( 2021-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Abstract: Adipose dysfunction may drive the development of insulin resistance, type 2 diabetes (T2D) and nonalcoholic (NA) fatty liver disease (NAFLD), comprising NA fatty liver and steatohepatitis (NAFL and NASH). Possible underlying mechanism comprise impaired lipid storage or mitochondrial oxidation favoring increased fatty acid flux to other tissues. Thus, we examined subcutaneous (SAT) and visceral adipose tissue (VAT) mitochondrial capacity in humans with different degrees of insulin resistance and histologically proven NAFLD. Obese people without NAFL (OBE-CON, n=20, 38±8 years, body mass index 53±6 kg/m2, 10% T2D), with NAFL (OBE-NAFL, n=20, 40±8 years, 51±5 kg/m2, 25% T2D) or NASH (OBE-NASH, n=20, 42±10 years, 51±6 kg/m2, 40% T2D) underwent metabolic phenotyping and tissue biopsies. O2 flux rates from different substrates were measured with high resolution respirometry in SAT and VAT. In VAT, maximal uncoupled respiration was lower in OBE-NAFL (least square means (LSM): 0.46 pmol*mg wet weight–1*s–1 [95% confidence interval 0.21;0.71], p & lt;0.05) and OBE-NASH (LSM: 0.51 [0.26;0.76], p & lt;0.001) compared to OBE-CON. Similar differences were seen for state 3 respiration related to complex I (glutamate) or combined complex I and II activity (succinate). In Pearson correlation analysis, combined complex I and II activity in VAT positively correlated with whole-body insulin sensitivity (M value; r= 0.29, p & lt;0.05). VAT mitochondrial content, as assessed from mitochondrial DNA copy number, was not different between the groups. Protein expression of electron transport chain complexes was similar in VAT and SAT of all groups, except for complex IV that tended to be lower in VAT in OBE-NASH than in OBE-CON (p=0.065). Of note, in SAT, oxidative capacity was comparable between groups despite a higher mitochondrial mass in OBE-NASH than in OBE-CON (p=0.045). In conclusion, oxidative capacity is downregulated in VAT, but not in SAT of obese humans with NAFLD, which may be related to the degree of insulin resistance. Disclosure K. Pafili: None. M. Schlensak: None. M. Roden: Advisory Panel; Self; Allergan plc, Bristol-Myers Squibb Company, Novo Nordisk A/S, Research Support; Self; Boehringer Ingelheim International GmbH, Danone Nutricia, Sanofi-Aventis Deutschland GmbH. S. Kahl: None. D. Pesta: None. K. Strassburger: None. L. Mastrototaro: None. J. Puetzer-furmanczak: None. B. Dewidar: None. T. Sarabhai: None. I. Esposito: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-1212-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
    detail.hit.zdb_id: 1501252-9
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  • 8
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    Impaired Hepatic Mitochondrial Capacity in Nonalcoholic Steatohepatitis Associated With Type 2 Diabetes
    American Diabetes Association ; 2022
    In:  Diabetes Care Vol. 45, No. 4 ( 2022-04-01), p. 928-937
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 45, No. 4 ( 2022-04-01), p. 928-937
    Abstract: Individuals with type 2 diabetes are at higher risk of progression of nonalcoholic fatty liver (steatosis) to steatohepatitis (NASH), fibrosis, and cirrhosis. The hepatic metabolism of obese individuals adapts by upregulation of mitochondrial capacity, which may be lost during the progression of steatosis. However, the role of type 2 diabetes with regard to hepatic mitochondrial function in NASH remains unclear. RESEARCH DESIGN AND METHODS We therefore examined obese individuals with histologically proven NASH without (OBE) (n = 30; BMI 52 ± 9 kg/m2) or with type 2 diabetes (T2D) (n = 15; 51 ± 7 kg/m2) as well as healthy individuals without liver disease (CON) (n = 14; 25 ± 2 kg/m2). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps with d-[6,6-2H2]glucose. Liver biopsies were used for assessing mitochondrial capacity by high-resolution respirometry and protein expression. RESULTS T2D and OBE had comparable hepatic fat content, lobular inflammation, and fibrosis. Oxidative capacity in liver tissue normalized for citrate synthase activity was 59% greater in OBE than in CON, whereas T2D presented with 33% lower complex II–linked oxidative capacity than OBE and higher H2O2 production than CON. Interestingly, those with NASH and hepatic fibrosis score ≥1 had lower oxidative capacity and antioxidant defense than those without fibrosis. CONCLUSIONS Loss of hepatic mitochondrial adaptation characterizes NASH and type 2 diabetes or hepatic fibrosis and may thereby favor accelerated disease progression.
    Type of Medium: Online Resource
    ISSN: 0149-5992
    URL: Article
    DOI: 10.2337/dc21-1758
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1490520-6
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  • 9
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    1777-P: Acute Hyperbaric Oxygen (HBO) Treatment Increases Hepatic Insulin Sensitivity and Muscle Reactive Oxygen Species in Type 2 Diabetes
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Diabetes mellitus type 2 (T2D) is characterized by insulin resistance of liver and skeletal muscle, which is at least partly due to impaired muscle mitochondrial function. Long-term HBO therapy, as applied for treating the diabetic foot syndrome, has been shown to improve blood glucose concentrations. To study the underlying mechanisms, we examined the short-term effect of HBO treatment on insulin sensitivity and mitochondrial oxidative capacity and production of reactive oxygen species (ROS) in a randomized, double blinded, placebo-controlled trial. Volunteers with type 2 diabetes (n=4; age 61±4 years; body mass index 30.2±2.2 kg/m2; HbA1c 7.0±0.7%) underwent two 2-hours sessions in a hyperbaric chamber of once with application of 100% oxygen (1.4 bar over atmospheric pressure [barO] for 20 min; HBO) and once with ambient air as placebo (21% oxygen; 1.4 barO; PLC). Tissue-specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps with stable isotope dilution, while muscle oxygen fluxes were measured with high resolution respirometry. After HBO treatment, hepatic insulin sensitivity was higher (insulin-mediated suppression of endogenous glucose production: 69.7±0.1% vs. PLC 55.3±3.2%, p & lt;0.05), whereas peripheral insulin sensitivity was comparable (2.0±0.3 vs. 2.2±0.3 mg*kg-1*min-1, p=0.24). Muscle ROS production markedly increased after HBO (increase in ROS: 73±3% vs. PLC -14±5%; p & lt;0.005), while mitochondrial oxidative capacity only tended to be lower after HBO. In conclusion, a single session of HBO treatment already improves hepatic insulin resistance and stimulates muscle ROS release, which may activate antioxidative defense, both of which could contribute to improved glycaemia upon chronic treatment. Disclosure T. Sarabhai: None. E. Anadol-Schmitz: None. H. Katsuyama: None. D.F. Markgraf: Research Support; Self; Sanofi. L. Busch: None. R. Guthoff: None. J. Schneppendahl: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1777-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 10
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    Monounsaturated fat rapidly induces hepatic gluconeogenesis and whole-body insulin resistance
    American Society for Clinical Investigation ; 2020
    In:  JCI Insight Vol. 5, No. 10 ( 2020-5-21)
    Details
    In: JCI Insight, American Society for Clinical Investigation, Vol. 5, No. 10 ( 2020-5-21)
    Type of Medium: Online Resource
    ISSN: 2379-3708
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1172/jci.insight.134520
    DOI: 10.1172/jci.insight.134520DS1
    DOI: 10.1172/jci.insight.134520DS2
    Language: English
    Publisher: American Society for Clinical Investigation
    Publication Date: 2020
    detail.hit.zdb_id: 2874757-4
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