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  • 1
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    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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    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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  • 3
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    Reduced Muscle Strength Is Associated With Insulin Resistance in Type 2 Diabetes Patients With Osteoarthritis
    The Endocrine Society ; 2021
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 106, No. 4 ( 2021-03-25), p. e1062-e1073
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 4 ( 2021-03-25), p. e1062-e1073
    Abstract: Type 2 diabetes is associated with a greater risk for musculoskeletal disorders, yet its impact on joint function remains unclear. Objective We hypothesized that patients with type 2 diabetes and osteoarthritis would exhibit musculoskeletal impairment, which would associate with insulin resistance and distinct microRNA profiles. Methods Participants of the German Diabetes Study with type 2 diabetes (T2D, n = 39) or normal glucose tolerance (CON, n = 27), both with (+OA) or without osteoarthritis (-OA) underwent intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp tests. Musculoskeletal function was assessed by isometric knee extension strength (KES), grip strength, range of motion (ROM), and balance skills, while neural function was measured by nerve conductance velocity (NCV). Arthritis-related symptoms were quantified using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, serum arthritis-related microRNA using quantitative polymerase chain reaction. Results Insulin sensitivity was lower in T2D+OA vs T2D-OA (4.4 ± 2.0 vs 5.7 ± 3.0 mg* kg–1*min–1) and in CON+OA vs CON-OA (8.1 ± 2.0 vs 12.0 ± 2.6 mg*kg–1,*min–1, both P  & lt; .05). In T2D+OA, KES and ROM were 60% and 22% lower than in CON+OA, respectively (both P  & lt; .05). Insulin sensitivity correlated positively with KES (r = 0.41, P  & lt; .05) among T2D, and negatively with symptom severity in CON and T2D (r = –0.60 and r = –0.46, respectively, P  & lt; .05). CON+OA and T2D+OA had inferior balance skills than CON-OA, whereas NCV was comparable in T2D+OA and T2D-OA. Expression of arthritis-related microRNAs was upregulated in T2D compared to CON, but downregulated in CON+OA compared to CON-OA (P  & lt; .05), and did not differ between T2D+OA and T2D-OA. Conclusion Musculoskeletal impairment and osteoarthritis-related symptoms are associated with insulin resistance. Type 2 diabetes can mask changes in arthritis-related microRNA profiles.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa912
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 4
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    Presentation_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-9-15)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-9-15)
    Abstract: Amino acids (AAs) are well known to be involved in the regulation of glucose metabolism and, in particular, of insulin secretion. However, the effects of different AAs on insulin release and kinetics have not been completely elucidated. The aim of this study was to propose a mathematical model that includes the effect of AAs on insulin kinetics during a mixed meal tolerance test. To this aim, five different models were proposed and compared. Validation was performed using average data, derived from the scientific literature, regarding subjects with normal glucose tolerance (CNT) and with type 2 diabetes (T2D). From the average data of the CNT and T2D people, data for two virtual populations (100 for each group) were generated for further model validation. Among the five proposed models, a simple model including one first-order differential equation showed the best results in terms of model performance (best compromise between model structure parsimony, estimated parameters plausibility, and data fit accuracy). With regard to the contribution of AAs to insulin appearance/disappearance (k AA model parameter), model analysis of the average data from the literature yielded 0.0247 (confidence interval, CI: 0.0168 – 0.0325) and -0.0048 (CI: -0.0281 – 0.0185) μU·ml -1 /(μmol·l -1 ·min), for CNT and T2D, respectively. This suggests a positive effect of AAs on insulin secretion in CNT, and negligible effect in T2D. In conclusion, a simple model, including single first-order differential equation, may help to describe the possible AAs effects on insulin kinetics during a physiological metabolic test, and provide parameters that can be assessed in the single individuals.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    URL: Article
    DOI: 10.3389/fendo.2022.966305
    DOI: 10.3389/fendo.2022.966305.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 5
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    Association of GDF15 levels with body mass index and endocrine status in β‐thalassaemia
    Wiley ; 2023
    In:  Clinical Endocrinology Vol. 99, No. 2 ( 2023-08), p. 182-189
    Details
    In: Clinical Endocrinology, Wiley, Vol. 99, No. 2 ( 2023-08), p. 182-189
    Abstract: GDF15 has emerged as a stress‐induced hormone, acting on the brain to reduce food intake and body weight while affecting neuroendocrine function. Very high GDF15 levels are found in thalassaemia, where growth, energy balance and neuroendocrine function are impaired. We examined the relationships between GDF15 and anthropometric measures and endocrine status in β‐thalassaemia. Design Cross sectional study. Patients All β‐thalassaemia patients attending the thalassaemia unit of Colombo North Teaching Hospital for blood transfusions. Measurements Anthropometric data, appetite scores, circulating GDF15, IGF, thyroid and reproductive hormone levels in 103 β‐thalassaemia patients were obtained. Results GDF15 levels were markedly elevated in thalassaemia patients (24.2‐fold with β‐thalassaemia major compared with healthy controls). Among patients with β‐thalassaemia major, the relationship between GDF15 and body mass index (BMI) was curvilinear with all individuals with GDF15 levels above 24,000 pg/mL having a BMI below 20 kg/m 2 . After adjustment for BMI, age and Tanner stage, serum IGF1 concentrations correlated negatively with GDF15 in all thalassaemia patients ( β  = −.027, p  = .02). We found a significant positive relationship between GDF15 and gonadotropin (in both sexes) and testosterone (in males). Conclusions GDF15 levels were markedly elevated in patients with β‐thalassaemia and its association with BMI is consistent with the known effect of GDF15 to reduce body weight. The inverse association between GDF15 with IGF1 levels may reflect a neuroendocrine impact of GDF15 or an indirect effect via impaired nutritional state. The positive association with testosterone in males and gonadotropins in both sexes, was surprising and should prompt further GDF15 studies on the hypothalamic pituitary gonadal axis.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    URL: Article
    DOI: 10.1111/cen.v99.2
    DOI: 10.1111/cen.14897
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2004597-9
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  • 6
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    Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 10 ( 2021-11-29), p. 3251-3263
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 10 ( 2021-11-29), p. 3251-3263
    Abstract: It has traditionally been suggested that the early development of diabetic sensorimotor polyneuropathy (DSPN) is characterized by predominant and progressive injury to small nerve fibres followed by large fibre impairment. We alternatively hypothesized that small and large fibre damage due to DSPN in type 1 and type 2 diabetes could develop in parallel and may not only be progressive but also reversible. Participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 350/570) and age-matched glucose-tolerant control individuals (Control 1/Control 2: n = 114/190) were assessed using nerve conduction studies, thermal detection thresholds, vibration perception thresholds, neuropathy symptom scores, neuropathy disability scores and intraepidermal nerve fibre density (IENFD) in skin biopsies (type 1/type 2 diabetes: n = 102/226; Control 1/Control 2: n = 109/208). Subsets of participants with type 1/type 2 diabetes were followed for 5 years (n = 184/307; IENFD subset: n = 18/69). DSPN was defined by the Toronto Consensus criteria. At baseline, DSPN was present in 8.1% and 13.3% of the type 1 and type 2 diabetes groups, respectively. The most frequently abnormal tests in the lower limbs below or above the 2.5th and 97.5th centiles of the controls were the IENFD (13.7%) and individual nerve conduction studies (up to 9.4%) in type 1 diabetes participants and IENFD (21.8%), malleolar vibration perception thresholds (17.5%), and individual nerve conduction studies (up to 11.8%) in those with type 2 diabetes, whereas thermal detection threshold abnormalities did not differ between the control and diabetes groups. After 5 years, the highest progression rates from the normal to the abnormal range in type 2 diabetes participants were found for IENFD (18.8%) by −4.1 ± 2.8 fibres/mm, malleolar vibration perception threshold (18.6%) by 9.1 ± 20.2 µm and nerve conduction studies (15.0%) by 3.7 ± 1.5 points, while vice versa the highest regression rates were observed for neuropathy disability scores (11.2%) by −3.1 ± 1.3 points, sural nerve amplitudes (9.1%) by 4.7 ± 3.0 µV, IENFD (8.7%) by 1.4 ± 1.3 fibres/mm, and neuropathy symptom scores (8.2%) by −5.8 ± 1.6 points. In type 1 diabetes participants, no major progression was seen after 5 years, but subclinical DSPN regressed in 10.3%. These findings point to early parallel damage to both small and large nerve fibres in well-controlled recent-onset type 2 and, to a lesser extent, type 1 diabetes. After 5 years, peripheral nerve morphology and function and clinical measures progress to the abnormal range in type 2 diabetes, but initial nerve alterations are also reversible to a meaningful degree.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awab330
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 7
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    Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes
    Elsevier BV ; 2023
    In:  Nutrition, Metabolism and Cardiovascular Diseases Vol. 33, No. 9 ( 2023-09), p. 1785-1796
    Details
    In: Nutrition, Metabolism and Cardiovascular Diseases, Elsevier BV, Vol. 33, No. 9 ( 2023-09), p. 1785-1796
    Type of Medium: Online Resource
    ISSN: 0939-4753
    URL: Article
    DOI: 10.1016/j.numecd.2023.06.004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2050914-5
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  • 8
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    Lower Stearoyl-CoA Desaturase and Hormone Sensitive Lipase Gene Expression in Superficial Subcutaneous Adipose Tissue of Male, but Not Female, Patients with Type 2 Diabetes
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
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    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Mitochondrial gene expression in visceral (VAT) and lipogenesis in abdominal subcutaneous adipose tissue (SAT) are lower in insulin resistance (IR). Humans with hormone sensitive lipase (HSL) gene mutations are prone to type 2 diabetes (T2D). SAT is divided into deep (DSAT) and superficial SAT (SSAT). SSAT was speculated to be protective in T2D, but gender specificity is unknown. We hypothesized lower mitochondrial efficiency as well as lower markers of lipogenesis and lipolysis in SSAT only in male T2D patients vs. glucose-tolerant humans (CON), which may characterize dysfunctional SSAT. In 20 T2D and 20 CON matched for sex, BMI and age (female/male: 6/14 per group; 32±1 vs. 31±1 kg/m2, 52±2 vs. 54±2 years), we assessed M-values by euglycemic-hyperinsulinemic clamps, liver fat content (HCL) and VAT by MRS. In biopsies of SSAT, mitochondrial oxidative capacity was measured by respirometry, lipogenesis assessed from stearoyl-CoA desaturase (SCD) mRNA, lipolysis from adipocyte triglyceride lipase (ATGL) and HSL mRNA by RTqPCR. The insulin resistant T2D had 63% and 22% higher HCL (p & lt;0.01) and VAT (p & lt;0.05) than CON. In SSAT, T2D featured 20%, 50%, 70%, 49% reductions in oxidative capacity, SCD, ATGL and HSL mRNA (all p & lt;0.05). Gender segregated analyzes showed higher oxidative capacity only in females, whereas only ATGL was also lower in female T2D vs. CON. In T2D, VAT was 22% lower (p & lt;0.01) and HSL mRNA 70% higher (both p & lt;0.001) in female than in male participants. In conclusion, lower lipogenesis and lipolysis in SSAT of male T2D patients may lead to inadequate lipid storage in SSAT, thereby promoting ectopic fat storage as HCL and VAT. Disclosure K. Bódis: None. J. Lundbom: None. T. Jelenik: None. D.F. Markgraf: None. A. Strom: None. O.P. Zaharia: None. Y. Karusheva: None. V. Burkart: None. K. Müssig: None. Y. Kupriyanova: None. M. Ouni: None. J. Hwang: None. D. Ziegler: None. A. Schuermann: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. J. Szendroedi: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-2054-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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  • 9
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    Effects on Insulin Sensitivity, but Not on Mitochondrial Function Are Dependent on Insulin Resistance Status after High Intensity Interval Training
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: High intensity interval training (HIIT) is a time-efficient training approach to stimulate biogenesis in healthy populations. We hypothesized that HIIT would increase skeletal muscle insulin sensitivity due to improved muscle mitochondrial function in type 2 diabetes (T2D) patients and age- and BMI-matched controls (CON). We examined 18 sedentary male patients with T2D and 23 healthy male CON (age: 58±5 vs. 57±4 years, BMI: 31.4±2.4 vs. 30.4±2.3 kg.m-2) that were enrolled in a 12-week HIIT cycling protocol. CON were further grouped in insulin-sensitive (IS) and -resistant (IR) (baseline M in mg.kg-1.min-1; 7.4 ± 1.3 vs. 4.2 ± 1.1, p & lt;0.001). Two-step hyperinsulinemic-euglycemic clamps, skeletal muscle biopsies for high resolution respirometry and magnetic resonance spectroscopy for liver fat quantification were performed. After 12 weeks of HIIT, T2D and IR CON increased their insulin sensitivity (3.9±1.9 vs. baseline: 2.7±1.6, p=0.02 and 5.5±2.1 vs. 4.2 ± 1.1, p=0.03, respectively), which returned to baseline after detraining. T2D and IR CON increased suppression of endogenous glucose production (EGP) during the high-insulin clamp (T2D: 91 ± 14% vs. baseline: 76 ± 11%, p=0.003 and IR CON: 107 ± 13% vs. 94 ± 14%, p=0.04). IR CON also increased suppression of lipolysis during the low-insulin clamp (82 ± 9 vs. 84 ± 8%, p=0.04). In T2D liver fat was decreased by 17% and remained decreased after detraining. Liver fat content remained unchanged by HIIT training in both CON groups. Muscle maximal uncoupled respiration increased in T2D and CON by 44% and 48%, respectively, at 12 weeks and remained increased after detraining in all groups (p & lt;0.01). We conclude that at the same level of insulin resistance HIIT training improved hepatic and peripheral insulin sensitivity in patients with T2D and insulin resistant controls whereas changes in mitochondrial function occurred irrespective of insulin resistance status. Disclosure M. Apostolopoulou: None. D. Pesta: None. Y. Karusheva: None. S. Gancheva: None. T. Jelenik: None. A. Bierwagen: None. K. M ssig: None. J. Szendroedi: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-69-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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  • 10
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    An 8-week diet high in cereal fiber and coffee but free of red meat does not improve beta-cell function in patients with type 2 diabetes mellitus: a randomized controlled trial
    Springer Science and Business Media LLC ; 2018
    In:  Nutrition & Metabolism Vol. 15, No. 1 ( 2018-12)
    Details
    In: Nutrition & Metabolism, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2018-12)
    Type of Medium: Online Resource
    ISSN: 1743-7075
    URL: Article
    DOI: 10.1186/s12986-018-0324-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2160376-5
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