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Continuous monitoring of the subcutaneous glucose level in freely moving normal and diabetic rats and in humans with Type I diabetes
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-1342-369X
2002 (English)In: Diabetes Technology and Therapeutics, ISSN 1520-9156, Vol. 4, no 3, 305-312 p.Article in journal (Refereed) Published
Abstract [en]

Laboratory animals are extensively used in diabetic research. However, it is not known whether the glucose dynamics in laboratory animals are similar to the dynamics in humans. The aim of the present study is to see whether the Medtronic MiniMed continuous subcutaneous glucose monitoring system can be used to record fluctuations of the glucose level in freely moving normal and insulin-treated diabetic rats. The monitoring system was applied during 3 days to normal and diabetic hyperglycemic and hypoglycemic rats treated with insulin implants. Corresponding data from type 1 diabetic patients with poor glycemic control were selected retrospectively in order to note the similarities and differences. In normal rats the subcutaneous glucose level varied slightly (median = 111 mg/dL). In hyperglycemic rats the subcutaneous glucose values fluctuated markedly around a median of 226 mg/dL. The fluctuations formed a short-wave pattern with a low amplitude, superimposed on a long-wave pattern with a high amplitude. The subcutaneous glucose profile seen in type 1 diabetic patients (median = 180 mg/dL) was similar to that observed in hyperglycemic rats. In hypoglycemic rats, the subcutaneous glucose level fluctuated moderately around a median of 55 mg/dL. In these rats the fluctuations formed a short-wave pattern with low amplitude, without any obvious long-wave pattern. The subcutaneous glucose values conformed to corresponding blood glucose measurements. We conclude that the Medtronic MiniMed continuous glucose monitoring system can be used to record the subcutaneous glucose level over time in freely moving rats.

Place, publisher, year, edition, pages
2002. Vol. 4, no 3, 305-312 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14187DOI: 10.1089/152091502760098447OAI: oai:DiVA.org:liu-14187DiVA: diva2:22863
Available from: 2007-01-09 Created: 2007-01-09 Last updated: 2016-02-29
In thesis
1. Peripheral Hypoglycaemic Neuropathy in Type 1 Diabetic Rats: Morphologic and Metabolic Studies
Open this publication in new window or tab >>Peripheral Hypoglycaemic Neuropathy in Type 1 Diabetic Rats: Morphologic and Metabolic Studies
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hyperglycaemia caused by insulin deficiency is believed to play a major role in the de-velopment of neuropathy in diabetic patients. The clinical and pathological features of diabetic neuropathy vary considerably, although sensory and autonomic dysfunctions are the most common characteristics. Normalisation of the blood glucose level by ef-fective insulin treatment decreases the incidence of diabetic neuropathy in patients. However, intensive insulin therapy may result in more frequent hypoglycaemic epi-sodes than are provoked by less ambitious diabetes control. Neuropathy might also be induced by severe hypoglycaemia in diabetes or insulinoma. Accordingly, it seems that the diversity in clinical symptoms of diabetic neuropathy may be due to the combined effects of hyperglycaemia and hypoglycaemia. Based on that assumption, the general aim of this project was to study the relationship between severe hypoglycaemia and pe-ripheral neuropathy in diabetic rats. To understand how the development of neuropathy is related to glycaemic control, we needed to be aware of the glucose dynamics in the animal model that we used. The aim was to ascertain whether the diabetic rats were similar to type 1 diabetic patients with regard to such dynamics. To achieve that goal, we used a MiniMed continuous glucose monitoring system (CGMS®) to measure sub-cutaneous glucose in freely moving rats over a period of 72 hours. The glucose monitor worked well, and it showed that the insulin-treated diabetic BB/Wor rats with a hyper-glycaemic insulin regimen have a glycaemic status similar to that of type 1 diabetic patients with poor glycaemic control. The diabetic rats with a hypoglycaemic regimen generally had low blood glucose levels.

Prolonged hypoglycaemia led to axonal de- and regeneration of large myelinated fibres in vagus nerve destined to the laryngeal muscle. Axonal de- and regeneration was also observed in the gastrocnemius and sural nerves, although the frequency of degeneration was much lower in the sural nerve. Small myelinated and unmyelinated nerve fibres were normal in these nerves. These results suggest that hypoglycaemia preferentially damages muscle-related nerve fibres. In contrast, in the diabetic rats exposed to pro-longed hyperglycaemia, only the sural nerve exhibited decreased myelinated fibre diameter in the absence of obvious axonal degeneration.

In situ glucose measurements by microdialysis showed that the glucose concentrations in blood and subcutaneous tissue were similar in healthy, diabetic hyperglycaemic, and diabetic hypoglycaemic rats. In the healthy and hyperglycaemic animals, the lowest glucose level was found in the peripheral nerve. Moreover, in controls, the glucose level was lower in muscle than in blood. In hypoglycaemic rats, there were no signifi-cant differences in glucose concentrations between different tissues.

Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 973
Keyword
Diabetes Mellitu, Hypoglycaemia, Neuropathy, Morphology, Microdialysis, Glucose level
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-7978 (URN)91-85643-20-3 (ISBN)
Public defence
2006-12-15, Eken, Cell Biology, 581 85 Linköping, Camups US, 09:00 (English)
Opponent
Supervisors
Available from: 2007-01-09 Created: 2007-01-09 Last updated: 2016-02-29

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