| 1. |
- Lindholm, Eero, et al.
(författare)
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Diabetic Neuropathy assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy
- 2023
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Ingår i: Experimental and Clinical Endocrinology & Diabetes. - : Georg Thieme Verlag KG. - 1439-3646 .- 0947-7349. ; 131:4, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes is declining but it is not known if this is true also for diabetic neuropathy.Aim: To investigate the relationship between large fiber diabetic neuropathy and other diabetic complications.Materials and methods: Neuropathy, defined here as large fiber neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot using a standard VibroSense Meter and/or neuropathic symptoms, in 599 type 1 diabetic individuals. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications, were registered.Results: Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control persons without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two persons out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7x10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001).Conclusions: Despite recent changes in the incidence of diabetic complications, the onset of large fiber neuropathy follows that of retinopathy but precedes the onset of nephropathy in type 1 diabetes.
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| 2. |
- 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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| 3. |
- Ekman, Linnéa, et al.
(författare)
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Diagnostic contribution of multi-frequency vibrometry to detection of peripheral neuropathy in type 1 diabetes mellitus compared with nerve conduction studies
- 2024
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Aim The aim was to assess the use of multi-frequency vibrometry (MFV) in detecting diabetic peripheral neuropathy (DPN) in type 1 diabetes in comparison to nerve conduction studies (NCS) and neurothesiometer (NT). Our objectives were to examine how VPTs correlated with NCS parameters, evaluate the efficacy of MFV in distinguishing DPN as well as to investigate whether MFV procedure could be based on fewer frequencies.Methods Adults with type 1 diabetes with previous MFV examinations were recruited at Skane University Hospital in Malmo, Sweden, between 2018 and 2020. Participants were examined regarding nerve function in the lower limbs through MFV, NT and NCS.Results A total of 66 participants (28 women and 38 men) with a median age of 50 (39 to 64) years were included in the study. Through NCS assessment, 33 participants (50%) were diagnosed with DPN. We found negative correlations between VPTs and all NCS parameters, where the strongest correlation was found between sural nerve amplitude and the 125 Hz frequency of MFV. A combination of four frequencies, two low (4 and 8 Hz) and two high (125 and 250 Hz), showed the highest classification efficacy (AUC 0.83, 95% CI 0.73-0.93).Conclusion We conclude that a strong correlation exists between the sural nerve amplitude and the VPTs at 125 Hz and that VPT testing with MFV can be focused on only four frequencies instead of seven, thus shortening test time, to distinguish DPN in the lower limb.
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| 4. |
- Ekman, Linnea, et al.
(författare)
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Normative values of the vibration perception thresholds at finger pulps and metatarsal heads in healthy adults
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Aims To establish normative values of vibration perception thresholds (VPTs), using multi-frequency vibrometry at finger pulps and at metatarsal heads of the foot in healthy adults. We also aimed to investigate factors that could potentially affect VPTs such as age, sex, height, weight, foot- or handedness and skin temperature. Methods VPTs were examined in 924 healthy and randomly selected subjects in the southern Sweden (mean 46 years; 628 women and 296 men). Inclusion criterias were adult subjects (>18 years) in considerable health without diabetes mellitus or other nerve affecting disorders. VPTs were measured at the finger pulps of index and little finger, as well as the first and fifth metatarsal heads of the foot, through multi-frequency vibrometry using the VibroSense Meter® I device. Patient characteristics were recorded and skin temperature was measured before assessment of VPTs. Results We present normative values of VPTs for a large population of both male and female subjects in various ages. VPTs detoriated as age increased (0.09-0.59 dB per year; p<0.001), i.e. progressing with normal aging. Increasing skin temperature affected VPTs in finger pulps, but not at metatarsal heads, with -0.2 to -1.6 dB, i.e. vibration perception improved with higher temperatures. Height was only found to affect the VPTs of metatarsal heads (250 Hz: 0.42 dB per cm). Sex, weight and handedness did not affect the VPTs. Conclusion We investigated the normative values of VPTs and presented affecting factors as age, skin temperature and height. With these results, VPT testing through multi-frequency vibrometry is enabled to be used in a clinical practice as a diagnostic tool when investigating neuropathy and other neurological disorders.
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| 5. |
- Elgzyri, Targ, et al.
(författare)
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Healing below the ankle is possible in patients with diabetes mellitus and a forefoot gangrene
- 2021
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Ingår i: SAGE Open Medicine. - : Sage Publications. - 2050-3121. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Forefoot gangrene in patients with diabetes is a severe form of foot ulcers with risk of progress and major amputation. No large cohort studies have examined clinical characteristics and outcome of forefoot gangrene in patients with diabetes. The aim was to examine clinical characteristics and outcome of forefoot gangrene in patients with diabetes admitted to a diabetic foot centre. Methods: Patients with diabetes and foot ulcer consecutively presenting were included if they had forefoot gangrene (Wagner grade 4) at initial visit or developed forefoot gangrene during follow-up at diabetic foot centre. Patients were prospectively followed up until final outcome, either healing or death. The median follow-up period until healing was 41 (3-234) weeks. Results: Four hundred and seventy-six patients were included. The median age was 73 (35-95) years and 63% were males. Of the patients, 82% had cardiovascular disease and 16% had diabetic nephropathy. Vascular intervention was performed in 64%. Fifty-one patients (17% of surviving patients) healed after auto-amputation, 150 after minor amputation (48% of surviving patients), 103 had major amputation (33% of surviving patients) and 162 patients deceased unhealed. Ten patients were lost at follow-up. The median time to healing for all surviving patients was 41 (3-234) weeks; for auto-amputated, 48 (10-228) weeks; for minor amputated, 48 (6-234) weeks; and for major amputation, 32 (3-116) weeks. Conclusion: Healing without major amputation is possible in a large proportion of patients with diabetes and forefoot gangrene, despite these patients being elderly and with extensive co-morbidity.
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| 6. |
- Korhonen, Laura, Professor, 1974-, et al.
(författare)
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Multivariate analyses of immune markers reveal increases in plasma EN-RAGE in first-episode psychosis patients
- 2023
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Ingår i: Translational Psychiatry. - : Springer. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.
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| 7. |
- van Zuydam, Natalie, et al.
(författare)
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Genome-Wide Association Study of Peripheral Artery Disease
- 2021
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 2574-8300. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status. Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status. Results: We identified 5 genome-wide significant (P-association <= 5x10(-8)) associations with PAD in 449 548 (N-cases=12 086) individuals of European ancestry near LPA (lipoprotein [a]), CDKN2BAS1 (CDKN2B antisense RNA 1), SH2B3 (SH2B adaptor protein 3) - PTPN11 (protein tyrosine phosphatase non-receptor type 11), HDAC9 (histone deacetylase 9), and CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit) loci (which overlapped previously reported associations). Meta-analysis with variants previously associated with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the CCSER1 (coiled-coil serine rich protein 1) locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32-1.74], P-diabetes=2.5x10(-9), P-interactionwithdiabetes=5.3x10(-7)). Furthermore, in smokers, rs12910984 at the CHRNA3 locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11-1.19], P-smokers=9.3x10(-10), P-interactionwithsmoking=3.9x10(-5)). Conclusions: Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.
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| 8. |
- Vanaveski, Taavi, et al.
(författare)
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PGC-1 alpha Signaling Increases GABA(A) Receptor Subunit alpha 2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice
- 2021
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Ingår i: Frontiers in Molecular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5099. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1 alpha expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of gamma-aminobutyric acid (GABA) type A receptor-alpha 2 subunit (GABAR alpha 2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1 alpha in neurons. Along with this, GABAR alpha 2 expression was enhanced in the hippocampus of the PGC-1 alpha Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABAR alpha 2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1 alpha Tg mice compared with controls. To study whether drugs acting on PPAR gamma can affect GABAR alpha 2, we employed pioglitazone that elevated GABAR alpha 2 expression in primary cultured neurons. Similar results were obtained using the specific PPAR gamma agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1 alpha regulates GABAR alpha 2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABAR alpha 2 expression via the PPAR gamma/PGC-1 alpha system.
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