| 1. |
- Golster, Helena, et al.
(författare)
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Testing microvascular function in children and adolescents with diabetes using laser Doppler perfusion imaging : implications on flow models and measurement sites
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the present study was to examine if functional impairment of the skin microvasculature is present in young diabetic patients with and without neurophysiological signs of nerve dysfunction. Dorsal foot skin blood flow was measured in young diabetics and controls using laser Doppler perfusion irnaging (LDPI). Blood flow was- measured during supine resting flow, during change in posture and during post occlusive hyperemia. Peripheral nerve function was measured by electrophysiological studies of peroneal and sural nerve conduction. Fifty seven (57%) percent of the diabetic patients had abnormal nerve conduction in two or several nerves. Diabetics with poor metabolic control (HbAlc > 7,5 %) showed an increase in supine resting blood flow compared to better regulated diabetics and controls. No other differences in skin blood flow between diabetics and controls were seen. During change in posture, blood flow increased instead of decreased in a majority of the study subjects. Low resting blood !low levels are suggested to contribute to this absence of postural vasoconstrictor response. It is concluded that nerve conduction defects arc much more common than microvascular abnormalities measured by LDPI in the present models in young diabetic patients. Our recommendation is to increase basal resting flow before applying vasoconstricting models in yotmg subjects when using LDPI in low flow areas, as the foot skin.
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| 2. |
- Gölster, Helena, 1965-, et al.
(författare)
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Impaired microvascular function related to poor metabolic control in young patients with diabetes
- 2005
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 25:2, s. 100-105
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to identify whether young patients with type 1 diabetes using modern multiple insulin injection therapy (MIT) have signs of microvascular dysfunction and to elucidate possible correlations with various disease parameters. Skin blood flow on the dorsum of the foot was measured with laser Doppler perfusion imaging in 37 patients (age 10–21 years, disease duration 6·0–16 years) and 10 healthy controls. Measurements were performed at rest, after change in posture (the leg was lowered below heart level) and during postocclusive hyperaemia. Following a change in posture blood flow increased instead of decreased in a majority of the study subjects. Patients with acute HbA1c >7·5% (n = 22) had an increase in skin blood flow at rest and a significantly reduced blood flow when the leg was lowered below heart level as compared with patients with HbA1c <7·5% (0·26 V versus 0·17 V, P<0·01 and 0·12 V versus 0·23 V, P<0·05, respectively) and healthy controls. Following occlusion of the macrocirculation for 3 min a small non-significant decrease in the hyperaemic response was seen in the patients. The postocclusive hyperaemic response and the venoarteriolar reflex were not correlated to duration of disease, long-term metabolic control or electrophysiological signs of peripheral nerve dysfunction. It is concluded that signs of microvascular dysfunction related to poor metabolic control are present in young patients with MIT treatment and rather well-controlled diabetes. Low resting blood flow levels are suggested to contribute to the absence of postural vasoconstrictor response.
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| 3. |
- Hyllienmark, Lars, et al.
(författare)
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Abnormal cold perception in the lower limbs : a sensitive indicator for detection of polyneuropathy in patients with type 1 diabetes mellitus
- 2009
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 16, s. 429-429
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic peripheral neuropathy differs in type 1 and type 2 diabetes. The aim of this study was to evaluate how signs and symptoms of neuropathy correlated with defects in motor and sensory nerve conduction velocity (MCV and SCV) and sensory perception thresholds in patients with type 1 diabetes. MCV and SCV in peroneal and sural nerves and vibratory, warm and cold perception thresholds (VPT, WPT, CPT) were evaluated in the lower limbs of 127 patients (42+/-7.9 years old, duration of diabetes, 16+/-11 years and HbA1c, 7.7+/-1.4%). The results were compared with clinical findings (neuropathy impairment assessment, NIA) and sensory symptoms (neurological symptom assessment, NSA). Sensory symptoms were present in 24% of patients, 91% had at least one abnormal finding in the neurological examination and 84% had abnormal nerve conduction. The greatest deviation from normal was observed for CPT on the dorsum of the foot and peroneal MCV. NIA and NSA correlated with all electrophysiological measurements in the foot and big toe. It is concluded that clinical findings correlate well with electrophysiological abnormalities in patients with type 1 diabetic neuropathy. An elevated CPT for the foot was the most pronounced sensory defect.
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| 4. |
- Hyllienmark, Lars, et al.
(författare)
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Early Electrophysiological Abnormalities and Clinical Neuropathy A prospective study in patients with type 1 diabetes
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:10, s. 3187-3194
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThe aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSFifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20 +/- 5.3 years (range 10-31 years).RESULTSAt baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P andlt; 0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA(1c) (R-2 = 48%, odds ratio 7.9, P andlt; 0.002) followed by peroneal MCV at baseline (R-2 = 38%, odds ratio 0.6, P andlt; 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA(1c) and then only peroneal MCV at baseline entered significantly (R-2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA(1c) ( = 0.40, P andlt; 0.002) than with follow-up HbA(1c) ( = 0.034, P andlt; 0.007).CONCLUSIONSEarly defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA(1c) during the first years of the disease.
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| 5. |
- Hyllienmark, Lars, et al.
(författare)
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EEG abnormalities with and without relation to severe hypoglycaemia in adolescents with type 1 diabetes
- 2005
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 48:3, s. 412-419
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: The aim of the present study was to identify whether adolescents with type 1 diabetes receiving modern multiple insulin injection therapy (MIT) have abnormal EEGs, and to elucidate possible correlations with a history of severe hypoglycaemia, poor metabolic control and nerve conduction defects. Methods: We investigated 35 patients (age 14-19 years) with disease duration 7.6±4.6 years, and 45 healthy control subjects. EEG spectral components were obtained from 15-min recordings in resting, awake subjects. Nerve conduction was measured bilaterally in motor and sensory fibres in the median, peroneal and sural nerves. Results: The EEGs of patients showed an increase in slow activity (delta and theta) and a reduction in alpha peak frequency, both of which were most pronounced in the frontal regions (p<0.001). They also showed a decrease in fast activity, which was most pronounced bilaterally in the posterior temporal regions (alpha p<0.001, beta p<0.01, gamma p<0.001). A history of severe hypoglycaemia was correlated with a global increase in theta activity (p<0.01-0.05). Poor metabolic control, measured as acute and long-term HbA1c levels, was correlated with an increase in delta activity and a decrease in alpha peak frequency. The decrease in fast activity in the temporal regions was a separate type of abnormality because it had a different distribution, and was not correlated with the increase in delta/theta power, poor metabolic control or with hypoglycaemia. Conclusions/interpretation: Recurrent severe hypoglycaemia and poor metabolic control are risk factors for EEG abnormalities in adolescents with type 1 diabetes receiving MIT treatment. In addition, we found pronounced abnormalities in the temporal regions that were not related to these risk factors. © Springer-Verlag 2005.
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| 6. |
- Hyllienmark, Lars
(författare)
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Influence of metabolic disturbance on nervous function : clinical and experimental studies
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present work consists of clinical and experimental studies and describes some effects of metabolic disturbance on nervous function. It is an electrophysiological examination of both single cells and patients exposed to metabolic insult or disease. The patch-clamp technique has been used for measurements of whole-cell currents in rat brain slices and studies of nerve conduction has been used as a clinical test on peripheral nervous function in young patients with insulin-dependent diabetes mellitus (IDDM).The objective of the clinical studies was to find out to what extent young IDDM patients with multiple insulin injection therapy (MIT) still develop peripheral nerve dysfunction and to elucidate the reason why.The objective of the experimental studies was to evaluate the effect of metabolic disturbance - induced chemically or by anoxia - on the membrane potential and the ionic conductances in hippocampal CA1 pyramidal cells.It is concluded that(1) despite MIT-treatment and good metabolic control nerve dysfunction is still common in an unselected group of children and adolescents with IDDM(2) the most important risk factors for nerve dysfunction in IDDM arc increased height and poor long-term metabolic control(3) metabolic inhibition at 22-24°C or anoxia at 33-34°C causes hyperpolarization and changes in the function of several types of K+ channels in CA1 pyramidal cells(4) a change in membrane potential by a few millivolts inhibited the spontaneous impulse firing(5) a transient opening of tolbutamide-sensitive K+ channels could explain the increase in grest and the hyperpolarization observed in most cells during metabolic inhibition(6) by this mechanism the excitablity decreases which may diminish the energy demand in cortical cells during different types of metabolic insult.
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| 7. |
- Hyllienmark, Lars, et al.
(författare)
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Nerve conduction defects are retarded by tight metabolic control in type I diabetes
- 2001
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Ingår i: Muscle and Nerve. - 0148-639X .- 1097-4598. ; 24:2, s. 240-246
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Tidskriftsartikel (refereegranskat)abstract
- This follow-up study examines whether the development of nerve dysfunction is retarded by tight metabolic control in patients with type I diabetes mellitus. Seventy-one patients and 115 age-matched healthy control subjects underwent studies of nerve conduction in peroneal and sural nerves. The presence of diabetes was associated with a reduction in peroneal motor nerve conduction velocity (MCV) by 5.9 m/s, sural sensory nerve conduction velocity (SCV) by 3.4 m/s, and sural sensory nerve action potential (SNAP) amplitude by 22%. Dysfunction in peroneal MCV, sural SCV, and sural SNAP were related to long-term poor metabolic control. Eleven of 12 patients with HbA1c <6.5% had normal nerve conduction or abnormality in only one nerve as compared to 2 of 15 patients with HbA1c >8.0%. It is concluded that tight long-term metabolic control (HbA1c <6.5%) can retard nerve dysfunction in patients with type I diabetes mellitus and a mean disease duration of 12 years.
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| 8. |
- Nordwall, Maria, et al.
(författare)
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Early diabetic complications in a population of young patients with Type 1 diabetes mellitus despite intensive treatment
- 2006
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Ingår i: Journal of Pediatric Endocrinology & Metabolism. - : Walter de Gruyter GmbH. - 0334-018X .- 2191-0251. ; 19:1, s. 45-54
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To describe the prevalence of early complications in an unselected population of patients with type 1 diabetes mellitus (DM1) diagnosed in childhood with intensive insulin treatment from diagnosis.Methods: Eighty children and adolescents with DM1, age 7-22 years and DM1 duration >3 years, were studied. Neuropathy was defined as abnormal nerve conduction finding in ≥2 of 4 nerves (sural and peroneal nerves), nephropathy as albumin excretion rate ≥20 μg/min and retinopathy as all grades of retinal changes in fundus photographs.Results: The prevalence of neuropathy was 59%, of retinopathy 27% and of nephropathy 5% after 13 years DM1 duration. Mean (SD) long-term HbA1c was 8.4 (0.9)% (DCCT-corrected value).Conclusion: Even in a population with intensive insulin treatment from the beginning and fairly good metabolic control, the prevalence of subclinical neuropathy was high, while other diabetic complications were lower than usually reported.
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| 9. |
- Papadopoulou-Marketou, Nektaria, 1974-, et al.
(författare)
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Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy
- 2021
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Ingår i: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications.METHODS: Thirty-three type 1 diabetes patients, aged 20-35 years, and disease duration 20 ± 5.3 years were included. Along with clinical examination, neurophysiological measurements, routine biochemistry, plasma concentrations of TIMP-1, MMP-9 and NGAL were determined with immunoenzymatic techniques.RESULTS: TIMP-1 correlated with abnormal unilateral and bilateral vibratory sense foot perception (r = -0.49 and r = -0.51, respectively), foot neuropathy impairment assessment score (NIA; r = -0.55), neuropathy symptom assessment score (r = 0.42), microalbuminuria (r = 0.50) and eGFR (r = -0.45). MMP-9 correlated with impaired foot NIA (r = 0.51). Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively).CONCLUSIONS: This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes.
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