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Early glycemic control, age at onset and development of microvascular complications in childhood-onset type 1 diabetes: A population-based study in Northern Sweden
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
(English)Manuscript (Other academic)
URN: urn:nbn:se:umu:diva-5146OAI: diva2:144544
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2010-10-13Bibliographically approved
In thesis
1. Metabolic aspects on diabetic nephropathy
Open this publication in new window or tab >>Metabolic aspects on diabetic nephropathy
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.
Umeå University medical dissertations, ISSN 0346-6612 ; 831
Medicine, Medicin
National Category
Dermatology and Venereal Diseases
Research subject
Internal Medicine
urn:nbn:se:umu:diva-79 (URN)91-7305-407-0 (ISBN)
Public defence
2003-04-25, Umeå, 09:00
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved

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