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Metabolic aspects on diabetic nephropathy
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diabetic nephropathy (DN) is associated with morbidity and mortality due to cardiovascular disease and renal failure. This study focused on the impact of glycemic control on the development of DN and the metabolic consequences of DN. The euglycemic hyperinsulinemic clamp technique was used to assess insulin sensitivity and insulin clearance. Two different registries, the Diabetes Incidence Study in Sweden (DISS) and the Swedish Childhood Diabetes Registry, as well as questionnaires and data from medical records were used to study diabetic complications in population-based cohorts.

Microalbuminuria is an early marker of DN and may also be associated with impaired insulin sensitiv-ity in diabetic and non-diabetic subjects. We studied the relationship between insulin sensitivity and the degree of albuminuria in patients with type 1 diabetes and micro- or macroalbuminuria but normal glomerular filtration rate (GFR). We did not find a direct quantitative association between the degree of albuminuria and insulin resistance, arguing against a cause-effect relationship.

With progression of DN, a decline in GFR is seen. Patients with severe renal failure have both im-paired insulin sensitivity and insulin clearance. We studied insulin sensitivity and insulin clearance in type 1 diabetes patients with three different degrees of renal involvement (none, only albuminuria, and slightly reduced GFR, ~40-70 ml/min/1.73 m2, respectively). A clear reduction in insulin sensitivity in vivo, but not in insulin clearance, was seen in the group with reduced GFR, and concomitant changes in the levels of PTH, IGF-1, IL-6 and TNF-α were found. In parallel, cellular insulin sensitivity and insulin degradation were examined in vitro, in subcutaneous fat cells but no differences were found between the three groups of patients.

To study the occurrence of renal involvement in patients with modern diabetes treatment we moni-tored a cohort of young adults from the DISS-registry with onset of diabetes in 1987-88 at age 15-34 years. We found that ~7% of the patients had signs of renal involvement, i.e. incipient nephropathy (5%) and overt nephropathy (2%), after a median follow-up of ~9 years and the strongest risk markers were poor glycemic control (HbA1c) and high blood pressure. Patients with type 2 diabetes were most prone to have renal involvement in this age group.

Retrospectively, we studied 94 patients diagnosed with type 1 diabetes in 1981-1992 at age 0-14 years at the Umeå University Hospital. Incipient nephropathy and background retinopathy occurred in 18 and 45%, respectively, of the patients, during ~12 years of follow-up. Glycemic control, also during the first five years of diabetes, was a strong risk marker. Young age at onset of diabetes prolonged the time to development of microvascular complications.

Conclusion: Despite modern diabetes treatment some patients with diabetes develop renal involvement within the first ten years. Inadequate glycemic control, also early in the disease, is a risk marker as well as type 2 diabetes and high blood pressure. In patients with type 1 diabetes and diabetic neph-ropathy a slightly reduced GFR, but not albuminuria, is associated with insulin resistance. Concomi-tant changes in insulin-antagonistic hormones and cytokines may be involved.

Place, publisher, year, edition, pages
Umeå: Folkhälsa och klinisk medicin , 2003. , 68 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 831
Keyword [en]
Medicine
Keyword [sv]
Medicin
National Category
Dermatology and Venereal Diseases
Research subject
Internal Medicine
Identifiers
URN: urn:nbn:se:umu:diva-79ISBN: 91-7305-407-0 (print)OAI: oai:DiVA.org:umu-79DiVA: diva2:144545
Public defence
2003-04-25, Umeå, 09:00
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
List of papers
1. No direct link between albumin excretion rate and insulin resistance--a study in type 1 diabetes patients with mild nephropathy
Open this publication in new window or tab >>No direct link between albumin excretion rate and insulin resistance--a study in type 1 diabetes patients with mild nephropathy
2002 In: Hormone and metabolic research, Vol. 34, no 5, 254-9 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-5143 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
2. A small reduction in glomerular filtration is accompanied by insulin resistance in type I diabetes patients with diabetic nephrophathy
Open this publication in new window or tab >>A small reduction in glomerular filtration is accompanied by insulin resistance in type I diabetes patients with diabetic nephrophathy
2002 In: European Journal of Clinical Investigation, Vol. 32, no 2, 100-9 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-5144 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
3. Signs of renal in-volvement may appear early in young adults with diabetes despite modern diabetes management: Results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)
Open this publication in new window or tab >>Signs of renal in-volvement may appear early in young adults with diabetes despite modern diabetes management: Results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)
Show others...
Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:umu:diva-5145 (URN)
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
4. Early glycemic control, age at onset and development of microvascular complications in childhood-onset type 1 diabetes: A population-based study in Northern Sweden
Open this publication in new window or tab >>Early glycemic control, age at onset and development of microvascular complications in childhood-onset type 1 diabetes: A population-based study in Northern Sweden
(English)Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-5146 (URN)
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2010-10-13Bibliographically approved

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CiteExportLink to record
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Citation style
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