| 11. |
- Chisalita, Simona Ioana, et al.
(författare)
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Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control
- 2009
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 46:1, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to study, at the same glycemic control, how treatment with either the insulin secretagogue repaglinide or exogenous insulin aspart affects endogenous insulin secretion, plasma insulin and IAPP (islet amyloid polypeptide) levels, GH-IGF (growth hormone-insulin-like growth factor) axis and plasma lipoprotein concentrations in patients with type 2 diabetes. Five patients, age 65.0 +/- A 4.1 years (mean +/- A SE), body weight 82.5 +/- A 5.0 kg, BMI (body mass index) 27.7 +/- A 1.5 kg/m(2) were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, C-peptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment, the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higher during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment. Our results show that, at the same glycemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.
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| 12. |
- Cimini, Flavia Agata, et al.
(författare)
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High pro‑neurotensin levels in individuals with type 1 diabetes associate with the development of cardiovascular risk factors at follow‑up
- 2022
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 59:1, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Neurotensin (NT) is a gut hormone that promotes lipids absorption and controls appetite. Elevated circulating pro-NT, the stable precursor of NT, is associated with cardiovascular (CV) disease, metabolic syndrome (MS) and type 2 diabetes (T2D). Features of MS and insulin resistance are reported also in type 1 diabetes (T1D), with detrimental impact on the overall CV risk profile. Aims of the study were to evaluate plasma pro-NT in T1D patients and to test whether its levels are associated with and/or predictive of CV risk factors and overall risk profile.Methods: For this longitudinal retrospective study, we analyzed clinical data from 41 T1D individuals referring to the diabetes outpatient clinics at Sapienza University of Rome, Italy, collected at the baseline and after 10 years. Fasting plasma pro-NT levels were measured in T1D subjects at the baseline and in 34 age-, sex-, BMI-comparable healthy individuals recruited in the same period.Results: Pro-NT did not differ significantly between patients and controls (median[range] pro-NT: 156.3 [96.6-198.2] vs. 179.4 [139.7-230.7] pmol/L, p = 0.26). In T1D, greater fasting pro-NT associated with poor glycemic control at baseline and predicted increased waist circumference, reduced insulin sensitivity, dyslipidemia and hypertension at 10-year follow-up. High pro-NT predicted 10-year very-high CV risk with adjusted OR = 11 (95%C.I.: 1.4-94.5; p = 0.029).Conclusions: In T1D individuals, elevated pro-NT levels predict the development of adverse metabolic profile, which translates in higher CV risk profile at 10-year follow-up. Pro-NT represents a novel predictor/marker of CV risk factors in adults with T1D.
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| 13. |
- Dahlin, Lars B., et al.
(författare)
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Improved metabolic control using glucose monitoring systems leads to improvement in vibration perception thresholds in type 1 diabetes patients
- 2020
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 57:4, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Few studies have examined how improved metabolic control might influence vibration perception thresholds (VPTs). The aim of this study was to evaluate if improved HbA1c can influence vibration thresholds in adults with type 1 diabetes (T1DM). Methods: VPTs were investigated at six frequencies (4–125 Hz) using VibroSense Meter in the sole of the foot at two occasions in 159 T1DM patients, at the heads of the first and fifth metatarsal bones, i.e. MTH1 and MTH5, respectively. The participants were divided into three groups: group A: HbA1c improved by more than 1 mmol/mol (n = 95), group B: HbA1c deteriorated by more than 1 mmol/mol (n = 48) and group C: HbA1c unchanged (± 1 mmol/mol) (n = 16) compared to baseline. Results: In group A, the mean z-score, reflecting the combined effect of all VPTs, improved being lower at the follow-up than at the baseline [0.2 (− 0.3 to 1.2) vs. −0.1 (− 0.7 to 0.8), p = 0.00002]. VPTs improved at 4 and 64 Hz at both MTH1 (metatarsal head 1) and MTH5. The VPTs at 125 Hz frequency improved at MTH5, but not at MTH1. No significant differences were seen in group B or group C. Conclusions: Lower HbA1c and lower VPTs in T1DM patients were associated with improved VPT, suggesting a reversible effect on nerve function by improved metabolic control.
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| 14. |
- Daneshpajooh, Mahboubeh, et al.
(författare)
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MC1568 improves insulin secretion in islets from type 2 diabetes patients and rescues β-cell dysfunction caused by Hdac7 upregulation
- 2018
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 55:12, s. 1231-1235
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Tidskriftsartikel (refereegranskat)abstract
- Aims: It has in recent years been established that epigenetic changes contribute to β-cell dysfunction and type 2 diabetes (T2D). For example, we have showed that the expression of histone deacetylase 7 (HDAC7) is increased in pancreatic islets of individuals with T2D and that increased levels of Hdac7 in β-cells impairs insulin secretion. The HDAC inhibitor MC1568 rescued this secretory impairment, suggesting that inhibitors specific for HDAC7 may be useful clinically in the treatment of T2D. The aim of the current study was to further explore HDAC7 as a novel therapeutic target in T2D. Methods: Hdac7 was overexpressed in clonal β-cells followed by the analysis of insulin secretion, mitochondrial function, as well as cell number and apoptosis in the presence or absence of MC1568. Furthermore, the effect of MC1568 on insulin secretion in human pancreatic islets from non-diabetic donors and donors with T2D was also studied. Results: Overexpression of Hdac7 in clonal β-cells significantly reduced insulin secretion, mitochondrial respiration, and ATP content, while it increased apoptosis. These impairments were all rescued by treatment with MC1568. The inhibitor also increased glucose-stimulated insulin secretion in islets from donors with T2D, while having no effect on islets from non-diabetic donors. Conclusions: HDAC7 inhibition protects β-cells from mitochondrial dysfunction and apoptosis, and increases glucose-stimulated insulin secretion in islets from human T2D donors. Our study supports specific HDAC7 inhibitors as novel options in the treatment of T2D.
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| 15. |
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| 16. |
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| 17. |
- Ekholm, Ella, et al.
(författare)
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Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection.
- 2011
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429.
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P < 0.001). No such correlation was seen for insulin and GLP-1. Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for insulin and GLP-1. Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients.
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| 18. |
- Ekholm, Ella, et al.
(författare)
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No signs of progressive beta cell damage during 20 years of prospective follow-up of autoantibody-negative diabetes.
- 2012
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429. ; 49, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- Both type 1 and type 2 diabetes are considered to be associated with different degrees of progressive beta cell damage. However, few long-term studies have been made. Our aim was to study the clinical course of 20 years of diabetes disease, including diabetes progression, comorbidity, and mortality in a prospectively studied cohort of consecutively diagnosed diabetic patients. Among all 233 patients diagnosed with diabetes during 1985-1987 in Malmö, Sweden, 50 of 118 surviving patients were followed-up after 20 years. The age at diagnose was 42.3 ± 23.1 and 57.5 ± 13.6 years for antibody-positive and antibody-negative patients, respectively. HbA1c and plasma lipids were analyzed with regard to metabolic control. Islet antibody-negative patients at diagnosis had highly preserved C-peptide levels after 20 years in contrast to antibody-positive patients (antibody negative: C-peptide 0 years 0.78 ± 0.47 and 20 years 0.70 ± 0.46 (nmol/l), P = 0.51 and antibody positive: C-peptide 0 years 0.33 ± 0.35 and 20 years 0.10 ± 0.18; P < 0.001. Islet antibodies but not age, BMI, or C-peptide at diagnosis were predictors of C-peptide levels at 20 years when analyzed by logistic regression (P < 0.05). HbA1c did not differ between the groups after 20 years. The 20-year mortality was higher among antibody-negative patients, dependent on the higher age at diagnosis in this group (number of deaths: antibody positive: 18 of 56 vs. antibody negative: 109 of 188, P < 0.001). Of the deceased, 79% had died from diseases or complications that may be associated with diabetes. We found no progressive beta cell damage in autoantibody-negative diabetes at a 20-year follow-up of the clinical course of diabetes.
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| 19. |
- Eriksson, M. I., et al.
(författare)
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Haptoglobin genotype and its relation to asymptomatic cerebral small-vessel disease in type 1 diabetes
- 2023
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 60:6, s. 749 - 756
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles’ association with SVD. Methods: This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts). Results: SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74–83], 75 [70–80], and 75 [72–81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46–2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy. Conclusions: Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.
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| 20. |
- Eriksson, Olof, et al.
(författare)
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Pancreatic imaging using an antibody fragment targeting the zinc transporter type 8 : a direct comparison with radio-iodinated Exendin-4
- 2018
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Ingår i: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 55:1, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The zinc transporter 8 (ZnT8) has been suggested as a suitable target for non-invasive visualization of the functional pancreatic beta cell mass, due to both its pancreatic beta cell restricted expression and tight involvement in insulin secretion.METHODS: In order to examine the potential of ZnT8 as a surrogate target for beta cell mass, we performed mRNA transcription analysis in pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was radiolabeled with iodine-125, and evaluated by in vitro autoradiography in insulinoma and pancreas as well as by in vivo biodistribution. The evaluation was performed in a direct comparison with radio-iodinated Exendin-4.RESULTS: Transcription of the ZnT8 mRNA was higher in islets of Langerhans compared to exocrine tissue. Ab31 targeted ZnT8 in the cytosol and on the plasma membrane with 108 nM affinity. Ab31 was successfully radiolabeled with iodine-125 with high yield and > 95% purity. [(125)I]Ab31 binding to insulinoma and pancreas was higher than for [(125)I]Exendin-4, but could only by partially competed away by 200 nM Ab31 in excess. The in vivo uptake of [(125)I]Ab31 was higher than [(125)I]Exendin-4 in most tissues, mainly due to slower clearance from blood.CONCLUSIONS: We report a first-in-class ZnT8 imaging ligand for pancreatic imaging. Development with respect to ligand miniaturization and radionuclide selection is required for further progress. Transcription analysis indicates ZnT8 as a suitable target for visualization of the human endocrine pancreas.
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