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  • 1
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    Metabolic Factors Predict Changes in Endothelial Function During the Early Course of Type 1 and Type 2 Diabetes
    The Endocrine Society ; 2022
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 107, No. 10 ( 2022-09-28), p. e4167-e4176
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 10 ( 2022-09-28), p. e4167-e4176
    Abstract: Endothelial dysfunction may occur early in the development of cardiovascular and metabolic diseases; however, it remains often underestimated and studies rarely discriminate between diabetes types. We have examined endothelial function and its determinants during the early course of type 1 and type 2 diabetes. Methods Caucasian participants of the prospective German Diabetes Study (GDS) with known diabetes duration & lt;1 year (n = 398) or without diabetes, but of similar age, body mass index (BMI) and sex distribution (n = 109), underwent measurements of flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD). Whole-body insulin sensitivity (M-value) was assessed by hyperinsulinemic–euglycemic clamps and physical fitness (VO2max) by spiroergometry. A subset of individuals with type 1 or type 2 diabetes (n = 108) was re-evaluated after 5 years. Results At baseline, neither FMD nor NMD differed between people with diabetes and the matched glucose-tolerant groups. At the 5-year follow-up, decline in FMD (–13.9%, P = .013) of persons with type 2 diabetes was independent of age, sex, and BMI, but associated with baseline adipose tissue insulin resistance and indices of liver fibrosis. The M-value decreased in both type 1 and type 2 diabetes groups by 24% and 15% (both P  & lt; .001, respectively) over 5 years. Higher HbA1c, lower M-value, and lower VO2max at baseline was associated with lower FMD in both type 1 and type 2 diabetes. Conclusion Endothelial function decreases during the early course of type 2 diabetes. In addition to age and BMI, insulin sensitivity at diagnosis was the best predictor of progressive impairment in endothelial function in type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgac480
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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  • 2
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    432-P: Role of Patatin-Like Phospholipase Domain–Containing 3 Gene for Kidney Dysfunction in Diabetes Endotypes
    American Diabetes Association ; 2023
    In:  Diabetes Vol. 72, No. Supplement_1 ( 2023-06-20)
    Details
    In: Diabetes, American Diabetes Association, Vol. 72, No. Supplement_1 ( 2023-06-20)
    Abstract: Recent studies identified distinct endotypes of diabetes with differences in metabolic features and in risk for diabetes-related comorbidities. Of note, persons allocated to the severe insulin resistant diabetes (SIRD) endotype, who show increased prevalence of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), are more frequently carriers of the G-allele in the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene. This SNP associates with increased risk of NAFLD yet the association between the presence of the PNPLA3 SNP and CKD remains controversial. The present study examined whether this SNP differently associates with CKD in endotypes of recent-onset diabetes. Participants with newly diagnosed diabetes (n=707) from the prospective German Diabetes Study underwent k-means clustering, genotyping, magnetic resonance spectroscopy to determine hepatocellular lipid content (HCL) and laboratory analyses to calculate the glomerular filtration rates (eGFR). SIRD had the lowest eGFR and highest HCL compared to severe insulin deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes clusters (all p & lt;0.05). HCL was negatively associated with eGFR (r=-0.287, p & lt;0.01) across all groups. Further stratification by PNPLA3 G-allele carrier status did not reveal any association between HCL and eGFR in any of the diabetes types, irrespective of G-allele carrier status. However, with declining eGFR the proportion of G-allele carriers increased from 44% for eGFR & gt;60 ml/min to 52% for eGFR & lt;60 ml/min (p & lt;0.05). In conclusion, increased hepatic lipid content is associated with reduced kidney function across all diabetes endotypes. This association is independent of the presence of the PNPLA3 polymorphism in newly diagnosed diabetes, but there might be role for PNPLA3 for the severity of CKD. Disclosure O.P. Zaharia: None. K. Strassburger: None. B. Knebel: None. Y. Kupriyanova: None. J. Kotzka: None. K. Bódis: None. M. Schön: None. M. Bombrich: None. C. Möser: None. K. Prystupa: Other Relationship; Berlin-Chemie AG. H. Al-Hasani: None. V. Schrauwen-Hinderling: None. K. Jandeleit-Dahm: None. R. Wagner: Speaker's Bureau; Novo Nordisk, Sanofi. Advisory Panel; Daiichi Sankyo. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis. Consultant; TARGET PharmaSolutions, Inc. Research Support; Sanofi. Funding German Research Foundation; European Foundation for the Study of Diabetes; German Diabetes Association; German Federal Ministry of Education and Research; Heinrich Heine University
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-432-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
    detail.hit.zdb_id: 1501252-9
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  • 3
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    Precise diabetes diagnosis determines therapeutic strategies in patients with cardiovascular events
    Springer Science and Business Media LLC ; 2021
    In:  Der Diabetologe Vol. 17, No. 1 ( 2021-01), p. 32-35
    Details
    In: Der Diabetologe, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2021-01), p. 32-35
    Type of Medium: Online Resource
    ISSN: 1860-9716 , 1860-9724
    URL: Article
    DOI: 10.1007/s11428-020-00703-x
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2205087-5
    detail.hit.zdb_id: 3120267-6
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  • 4
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    An Empirical Approach to Derive Water T 1 from Multiparametric MR Images Using an Automated Pipeline and Comparison With Liver Stiffness
    Wiley ; 2024
    In:  Journal of Magnetic Resonance Imaging Vol. 59, No. 4 ( 2024-04), p. 1193-1203
    Details
    In: Journal of Magnetic Resonance Imaging, Wiley, Vol. 59, No. 4 ( 2024-04), p. 1193-1203
    Abstract: Water T 1 of the liver has been shown to be promising in discriminating the progressive forms of fatty liver diseases, inflammation, and fibrosis, yet proper correction for iron and lipid is required. Purpose To examine the feasibility of an empirical approach for iron and lipid correction when measuring imaging‐based T 1 and to validate this approach by spectroscopy on in vivo data. Study Type Retrospective. Population Next to mixed lipid‐iron phantoms, individuals with different hepatic lipid content were investigated, including people with type 1 diabetes ( N = 15, %female = 15.6, age = 43.5 ± 14.0), or type 2 diabetes mellitus ( N = 21, %female = 28.9, age = 59.8 ± 9.7) and healthy volunteers ( N = 9, %female = 11.1, age = 58.0 ± 8.1). Field Strength/Sequences 3 T, balanced steady‐state free precession MOdified Look‐Locker Inversion recovery (MOLLI), multi‐ and dual‐echo gradient echo Dixon, gradient echo magnetic resonance elastography (MRE). Assessment T 1 values were measured in phantoms to determine the respective correction factors. The correction was tested in vivo and validated by proton magnetic resonance spectroscopy ( 1 H‐MRS). The quantification of liver T 1 based on automatic segmentation was compared to the T 1 values based on manual segmentation. The association of T 1 with MRE‐derived liver stiffness was evaluated. Statistical Tests Bland–Altman plots and intraclass correlation coefficients (ICCs) were used for MOLLI vs. 1 H‐MRS agreement and to compare liver T 1 values from automatic vs. manual segmentation. Pearson's r correlation coefficients for T 1 with hepatic lipids and liver stiffness were determined. A P ‐value of 0.05 was considered statistically significant. Results MOLLI T 1 values after correction were found in better agreement with the 1 H‐MRS‐derived water T 1 (ICC = 0.60 [0.37; 0.76]) in comparison with the uncorrected T 1 values (ICC = 0.18 [−0.09; 0.44]). Automatic quantification yielded similar liver T 1 values (ICC = 0.9995 [0.9991; 0.9997]) as with manual segmentation. A significant correlation of T 1 with liver stiffness ( r = 0.43 [0.11; 0.67]) was found. A marked and significant reduction in the correlation strength of T 1 with liver stiffness ( r = 0.05 [−0.28; 0.38], P = 0.77) was found after correction for hepatic lipid content. Data Conclusion Imaging‐based correction factors enable accurate estimation of water T 1 in vivo. Level of Evidence 1 Technical Efficacy Stage 1
    Type of Medium: Online Resource
    ISSN: 1053-1807 , 1522-2586
    URL: Issue
    URL: Article
    DOI: 10.1002/jmri.v59.4
    DOI: 10.1002/jmri.28906
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 1497154-9
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  • 5
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    1300-P: Visceral Adipose Tissue Volume Is Increased in Severe Insulin Resistant Diabetes
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: Introduction & Objective: The severe insulin resistant diabetes (SIRD) endotype associates with markedly higher risk of metabolic dysfunction associated steatotic liver disease (MASLD). However, it is not known if ectopic lipid deposition is also higher in skeletal muscle or adipose tissue compartments than in other endotypes. Methods: Participants (n=697, known diabetes duration & lt;1 y) of the prospective German Diabetes Study (GDS) underwent 1H magnetic resonance spectroscopy for quantifying intramyocellular lipids (IMCL) in tibialis anterior muscle, intrahepatic lipids (IHL), visceral (VAT) and subcutaneous adipose tissue (SAT) volumes. The validated clustering algorithm used age, sex, BMI, HOMA-IR, HOMA-B, islet-directed autoantibodies. Results: As expected, SIRD (n=40) had the highest IHL (11±5%) compared to mean IHL values of 2-6% in moderate obesity-related (MOD, n=215), moderate age-related (MARD, n=237) and severe autoimmune diabetes clusters (SAID, n=193; all p & lt;0.01). Interestingly, SIRD presented with higher VAT than MOD, MARD and SAID (6089±2705 vs 3260±2310, 3056±1963, 1524±1401 cm3) even after adjustment for BMI (all p & lt;0.05). Also, SAT was higher in SIRD than MARD (27879±6777 vs 17127±6218 cm3, p & lt;0.05), while differences to other subtypes lost statistical significance upon correction for BMI. There were no differences in IMCL between subtypes. Overall, VAT correlated with cardiovascular risk (Framingham, r=0.661, p & lt;0.05), whole-body insulin sensitivity derived from hyperinsulinemic euglycemic clamp (r=-0.537, p & lt;0.05) and with beta cell function during intravenous glucose tolerance test (r=0.379, p & lt;0.05). Within SIRD, VAT was further associated with fasting glycemia (r=0.121, p=0.05) and fasting insulin resistance (HOMA-IR; r=0.372, p & lt;0.05). Conclusion: The increases in IHL and VAT underline their key role in the pathophysiology and progression of severely insulin resistant diabetes and shall help to refine subtyping approaches for precision diabetology. Disclosure O.P. Zaharia: None. Y. Kupriyanova: None. P. Bobrov: None. M. Schön: None. C. Möser: None. N. Trinks: None. D.M. Mendez Cardenas: None. S. Trenkamp: None. K. Bódis: None. V. Schrauwen-Hinderling: None. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. Speaker's Bureau; AstraZeneca. Funding EFSD Rising Star Award
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-1300-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
    detail.hit.zdb_id: 1501252-9
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  • 6
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    Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes
    American Diabetes Association ; 2023
    In:  Diabetes Vol. 72, No. 10 ( 2023-10-01), p. 1483-1492
    Details
    In: Diabetes, American Diabetes Association, Vol. 72, No. 10 ( 2023-10-01), p. 1483-1492
    Abstract: Intramyocellular lipid content (IMCL) is elevated in insulin-resistant humans, but it changes over time, and relationships with comorbidities remain unclear. We examined IMCL during the initial course of diabetes and its associations with complications. Participants of the German Diabetes Study (GDS) with recent-onset type 1 (n = 132) or type 2 diabetes (n = 139) and glucose-tolerant control subjects (n = 128) underwent 1H-MRS to measure IMCL and muscle volume, whole-body insulin sensitivity (hyperinsulinemic-euglycemic clamps; M-value), and cycling spiroergometry (VO2max). Subgroups underwent the same measurements after 5 years. At baseline, IMCL was ∼30% higher in type 2 diabetes than in other groups independently of age, sex, BMI, and muscle volume. In type 2 diabetes, the M-value was ∼36% and ∼62% lower compared with type 1 diabetes and control subjects, respectively. After 5 years, the M-value decreased by ∼29% in type 1 and ∼13% in type 2 diabetes, whereas IMCL remained unchanged. The correlation between IMCL and M-value in type 2 diabetes at baseline was modulated by VO2max. IMCL also associated with microalbuminuria, the Framingham risk score for cardiovascular disease, and cardiac autonomic neuropathy. Changes in IMCL within 5 years after diagnosis do not mirror the progression of insulin resistance in type 2 diabetes but associate with early diabetes-related complications. Article Highlights Intramyocellular lipid content (IMCL) can be elevated in insulin-resistant humans, but its dynamics and association with comorbidities remain unclear. Independently of age, sex, body mass, and skeletal muscle volume, IMCL is higher in recent-onset type 2, but not type 1 diabetes, and remains unchanged within 5 years, despite worsening insulin resistance. A degree of physical fitness modulates the association between IMCL and insulin sensitivity in type 2 diabetes. Whereas higher IMCL associates with lower insulin sensitivity in people with lower physical fitness, there is no association between IMCL and insulin sensitivity in those with higher degree of physical fitness. IMCL associates with progression of microalbuminuria, cardiovascular disease risk, and cardiac autonomic neuropathy.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-0353
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
    detail.hit.zdb_id: 1501252-9
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  • 7
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    Analysis of type 2 diabetes heterogeneity with a tree-like representation: insights from the prospective German Diabetes Study and the LURIC cohort
    Elsevier BV ; 2024
    In:  The Lancet Diabetes & Endocrinology Vol. 12, No. 2 ( 2024-02), p. 119-131
    Details
    In: The Lancet Diabetes & Endocrinology, Elsevier BV, Vol. 12, No. 2 ( 2024-02), p. 119-131
    Type of Medium: Online Resource
    ISSN: 2213-8587
    URL: Article
    DOI: 10.1016/S2213-8587(23)00329-7
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
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  • 8
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    Impact of mixed meal tolerance test composition on measures of beta-cell function in type 2 diabetes
    Springer Science and Business Media LLC ; 2021
    In:  Nutrition & Metabolism Vol. 18, No. 1 ( 2021-12)
    Details
    In: Nutrition & Metabolism, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2021-12)
    Abstract: Application of mixed meal tolerance tests (MMTT) to measure beta-cell function in long-term studies is limited by modification of the commercial products occurring over time. This study assessed the intra-individual reliability of MMTTs and compared the effects of liquid meals differing in macronutrient composition on the estimation of beta-cell function in type 2 diabetes (T2DM). Methods To test the reliability of MMTTs, 10 people with T2DM (age 58 ± 11 years, body mass index 30.0 ± 4.9 kg/m 2 ) received Boost® high Protein 20 g protein three times. For comparing different meals, another 10 persons with T2DM (58 ± 5 years, 31.9 ± 5.3 kg/m 2 ) ingested either Boost® high Protein 20 g protein or the isocaloric Boost® high Protein 15 g protein containing 35% less protein and 18% more carbohydrates. C-peptide, insulin and glucose release were assessed from the incremental area under the concentration time curve (iAUC) and the intra- and inter-individual variation of these parameters from the coefficients of variations (CV). Results Repetitive ingestion of one meal revealed intra-individual CVs for the iAUCs of C-peptide, insulin and glucose, which were at least 3-times lower than the inter-individual variation of these parameters (18.2%, 19.7% and 18.9% vs. 74.2%, 70.5% and 207.7%) indicating a good reliability. Ingestion of two different meals resulted in comparable intra-individual CVs of the iAUCs of C-peptide and insulin (16.9%, 20.5%). Conclusion MMTTs provide reliable estimation of beta-cell function in people with T2DM. Furthermore, moderate differences in the protein and carbohydrate contents in a standardized liquid meal do not result in relevant changes of C-peptide and insulin responses. Trial registration : Clinicaltrials.gov, Identifier number: NCT01055093. Registered 22 January 2010 – Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT01055093
    Type of Medium: Online Resource
    ISSN: 1743-7075
    URL: Article
    DOI: 10.1186/s12986-021-00556-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2160376-5
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  • 9
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    100-OR: Association of Recent Myocardial Infarction with Insulin Resistance and Fatty Liver Disease in Type 2 Diabetes
    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: Insulin resistance and nonalcoholic fatty liver disease (NAFLD) frequently associate with type 2 diabetes (T2D) and cardiovascular disease and worsen their prognosis. We hypothesized that people with recent myocardial infarction (MI) have lower left ventricular ejection fraction (EF) and higher degree of insulin resistance (IR) , hepatocellular lipid content (HCL) and risk of hepatic fibrosis than matched people without MI. Thus, participants of the “DIabetes and ST-Elevation MI (DISTEMI) Study” were examined 6-12 weeks after MI (MI+; n=53, 28% T2D) and compared to age-, sex-, BMI-matched people without MI (MI-; n=48, 31% T2D) . Insulin sensitivity was assessed during fasting (Homeostasis Model Assessment (HOMA) 2-IR) and hyperinsulinemic-euglycemic clamps (M-value) . EF, HCL and liver stiffness, associated with fibrosis stages, were quantified by 1H-magnetic resonance imaging, spectroscopy and elastography, respectively. MI+ had a lower EF (47±2 vs. 58±1 %, p & lt;0.0001) and M-value (7.3±0.4 vs. 8.2±0.4 mg*kg-1*min-1, p & lt;0.05) compared to MI-, which was mainly due to a difference between the T2D groups (EF: 39±6 vs. 52±2 %, p & lt;0.001; M-value: 4.2±0.5 vs. 6.1±0.6 mg*kg-1*min-1, p & lt;0.05) . HCL (3.4±0.8 vs. 5.8±0.9 %) and liver stiffness (2.2±0.1 vs. 2.3±0.1 kPa) were comparable between MI+ and MI-. HCL correlated negatively with M-value (r=-0.95, p & lt;0.05) and positively with systolic blood pressure (r=0.91, p & lt;0.05) in MI+ with T2D. In MI+ without T2D, HCL correlated positively with HOMA2-IR (r=0.58, p & lt;0.01) and BMI (r=0.53, p & lt;0.01) . In conclusion, recent myocardial infarction in people with type 2 diabetes associates with decreased ejection fraction and increased insulin resistance. The correlation between insulin resistance and liver fat content suggests that HCL can serve as a non-invasive cardiovascular marker and may identify persons with a worse outcome after myocardial infarction. Disclosure C.Möser: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. O.P.Zaharia: n/a. F.C.Michlotti: None. Y.Kupriyanova: None. V.Schrauwen-hinderling: None. P.Bobrov: None. V.Burkart: None. M.Kelm: Board Member; DGIM-Deutsche Geselleschaft für Innere Medizin, DGK-Deutsche Gesellschaft für Kardiologie, DSHF-Deutsche Stiftung für Herzforschung, ESC- European Society of Cardiology, Other Relationship; Abiomed , Bayer AG, diaplan, Kel Con GmbH, Research Support; Abiomed Europe GmbH, B.Braun, Edwards Lifesciences Corporation, European Union, IPP Med GmbH - Institut für Pharmakologie u. präventive Medizin GmbH, Mars Scientific Advisory Council (MSAC) , Medicure Inc., Microvision Medical. J.M.Szendroedi: Consultant; Boehringer Ingelheim International GmbH. Funding Research Network SFB 1116 of the German Research Foundation
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-100-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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