umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Does the autonomic nervous system play a role in the development of insulin resistance?: a study on heart rate variability in first-degree relatives of type 2 diabetes patients and control subjects
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
2003 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 20, no 5, 399-405 p.Article in journal (Refereed) Published
Abstract [en]

Aims To investigate dysregulation of the autonomic nervous system as a potential mechanism for early insulin resistance in the development of Type 2 diabetes.

Methods Thirteen healthy individuals with first-degree relatives with Type 2 diabetes (R) were compared with 14 control subjects without family history of diabetes (C), matched for age, body mass index and sex. An oral glucose tolerance test and a hyperinsulinaemic euglycaemic clamp were performed. Analysis of heart rate variability during rest, controlled breathing, an orthostatic manoeuvre and a standardized physical stress (cold pressor test (CPT)), were used to evaluate the activity of the autonomic nervous system.

Results Fasting blood glucose, HbA1c and serum insulin were similar in the R and C groups. The M-value, reflecting insulin sensitivity, did not differ significantly between the groups. Total spectral power and high-frequency power were lower in R during controlled breathing (P = 0.05 and P = 0.07, respectively), otherwise there were no significant differences between R and C in heart rate variability. However, low-frequency (LF)/high-frequency (HF) spectral power ratio during CPT, reflecting sympathetic/parasympathetic balance, was negatively associated with insulin sensitivity (r = −0.53, P = 0.006). When all subjects were divided into two groups by the mean M-value, the low M-value group displayed an overall higher LF/HF ratio (P = 0.04). HF power was lower in the low M-value group during controlled breathing and CPT (P = 0.01 and P = 0.03, respectively).

Conclusion An altered balance of the parasympathetic and sympathetic nervous activity, mainly explained by an attenuated parasympathetic activity, might contribute to the development of insulin resistance and Type 2 diabetes.

Place, publisher, year, edition, pages
2003. Vol. 20, no 5, 399-405 p.
Keyword [en]
insulin sensitivity, Type 2 diabetes, autonomic nervous system, heart rate variability, spectral analysis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:umu:diva-3845DOI: 10.1046/j.1464-5491.2003.00920.xPubMedID: 12752490OAI: oai:DiVA.org:umu-3845DiVA: diva2:142728
Available from: 2004-03-31 Created: 2004-03-31 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Neurohormonal mechanisms in insulin resistance and type 2 diabetes
Open this publication in new window or tab >>Neurohormonal mechanisms in insulin resistance and type 2 diabetes
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Insulin resistance usually occurs early in the development of type 2 diabetes. An altered balance in the autonomic nervous system and in certain endocrine and inflammatory pathways, might contribute to the development of insulin resistance. In diabetes, hyperglycemia further aggravates insulin resistance as well as beta cell dysfunction but the mechanisms causing this phenomenon, i.e. glucotoxicity, are not fully understood.

Insulin resistance can be demonstrated in healthy first-degree relatives of type 2 diabetes patients who also have a high risk of developing type 2 diabetes. Relatives and control subjects without family history of diabetes were studied with respect to insulin sensitivity and the activity in the autonomic nervous system (ANS) and in the cortisol axis. Levels of sex hormones, leptin and cytokines were analysed. Abdominal adipose tissue distribution was determined with computed tomography.

Male relatives had decreased testosterone levels and increased leptin levels. There was an inverse relationship between insulin sensitivity and leptin levels, and in males a positive association between insulin sensitivity and testosterone levels. A tendency to lower parasympathetic reactivity was found in the relatives using heart rate variability assessment. The sympathetic/parasympathetic ratio during stress provocation was inversely correlated to insulin sensitivity, measured with glucose clamp. The insulin-resistant subjects also exhibited an overall blunted reactivity in the ANS. Cortisol reactivity after stimulation with ACTH and CRH was lower in the relatives. The amount of visceral adipose tissue (VAT) was associated with insulin resistance and with heart rate at rest and during controlled breathing and it also correlated with heart rate and sympathetic/parasympathetic ratio after an orthostatic manoeuvre.

Type 2 diabetic subjects with good and poor glycemic control, respectively, and matched healthy control subjects were examined with respect to insulin sensitivity, cortisol axis activity and blood levels of leptin, sex hormones and the adipocyte-secreted inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Biopsies were taken from subcutaneous adipose tissue for determination of adipocyte size. Diabetes subjects were more insulin-resistant than controls and diabetics with poor control exhibited the highest degree of insulin resistance. This group also had the highest levels of TNF-α, morning serum cortisol and non-esterified fatty acids (NEFA). In correlation analyses, significant associations were seen between glycemic level and insulin resistance, TNF-α, IL- 6 and serum cortisol levels. Insulin resistance was positively correlated to NEFA levels, TNF-α and ACTH-stimulated cortisol levels. Adipocyte size was associated with insulin resistance and levels of IL-6 and leptin.

The findings support a connection between insulin resistance and VAT amount, activity in the ANS and blood levels of hormones and adipocyte-derived molecules. Dysregulation in the complex interplay between such factors may contribute to the early pathogenesis of insulin resistance and type 2 diabetes. Adipokines and the cortisol system can also potentially aggravate hyperglycemia in patients with manifest type 2 diabetes.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2004. 59 p.
Identifiers
urn:nbn:se:umu:diva-225 (URN)91-7305-591-3 (ISBN)
Public defence
2004-04-24, 09:00
Opponent
Available from: 2004-03-31 Created: 2004-03-31 Last updated: 2010-08-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Lindmark, StinaWiklund, UrbanBjerle, PEriksson, JW
By organisation
MedicineClinical PhysiologyCentre for Biomedical Engineering and Physics (CMTF)
In the same journal
Diabetic Medicine
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 213 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf