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Long term complications in juvenile diabetes mellitus
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background/aim. The incidence of microvascular complications has been reported to be unchanged the last decades. However, in randomized clinical trials it has been shown that improved metabolic control can reduce the development of long term complications. It has been debated whether it is possible to achieve the same results in an unselected population. In a previous study we found a decreased incidence of overt nephropathy, but unchanged incidence of severe laser treated retinopathy in a population of patients with type 1 diabetes diagnosed in childhood. The aim of the present study was to investigate the incidence 10 years later in the same population and to analyse the importance of possible risk factors. In another previous study we found a high prevalence of subclinical neuropathy among young diabetic patients despite intensive insulin therapy since diagnosis. The aim of the present study was to examine if intensive treatment is more effective in preventing early diabetic complications other than neuropathy. The incidence of type 1 diabetes has doubled in Sweden the last decades. The reason must be environmental factors. These, as well as more intensive insulin regimens from onset of diabetes, might also lead to different disease process. We wanted to analyse if clinical characteristics at onset had changed the last 25 years and if there was any secular trend of C-peptide secretion. We also intended to investigate if longer persistence of C-peptide secretion could be of importance for prevention of long term complications.

Methods. The whole study population consisted of all 478 patients with type 1 diabetes diagnosed before the age of 15 during the years 1961 - 2000, living in the catchment area of the Paediatric Clinic, University Hospital, Linköping, Sweden. For the statistical analysis the population was divided into five–year cohorts according to time of onset of diabetes. The cumulative proportion of severe retinopathy and overt nephropathy in 269 patients with onset of diabetes 1961 - 1985 was computed with survival analysis. Multivariable regression models were used to analyse the importance of metabolic control, diabetes duration, blood pressure, smoking, BMI, lipids and persisting C-peptide secretion. The prevalence of all grades of retinal changes, nephropathy and neuropathy, defined as abnormal nerve conduction, was estimated in the late 1990s in a subgroup of 80 children and adolescents with mean 13 years of diabetes duration. Clinical characteristics at onset, duration of partial remission and regularly measurements of fasting and stimulated C-peptide secretion the first five years after onset were analysed in 316 patients with onset of diabetes 1976 - 2000.

Results. The cumulative proportion of severe laser treated retinopathy showed a significant declining trend the last decades. The decrease was significant between the oldest cohort with diabetes onset 1961 - 1965 and the cohorts with diabetes onset 1971 - 1975 and 1976 - 1980. The cumulative proportion of overt nephropathy also declined with a significant decrease between the oldest cohorts and all the following cohorts. After 25 years of diabetes duration it was 30% and 8% in the two oldest cohorts respectively and remained largely unchanged after 30 years. Diabetes duration and long term HbA1c were the only significant independent risk factors for both retinopathy and nephropathy. The risk of overt nephropathy increased substantially when HbA1c was above 8.5%, while the risk of severe retinopathy increased already when HbA1c exceeded 7.5%. The prevalence of neuropathy was 59%, of retinopathy 27% and of nephropathy 5% in the population of young patients after mean 13 years of diabetes duration. During the last 25 years the clinical characteristics at onset were unchanged as well as duration of partial remission and magnitude and persistence of C-peptide secretion.

Conclusions. In this unselected population the cumulative proportion of severe retinopathy and overt nephropathy decreased over the last decades. Diabetic nephropathy has probably been prevented and not just postponed. Good glycaemic control was the most important factor to avoid complications, with the necessity of a lower level of HbA1c to escape retinopathy than nephropathy. Intensive insulin regimens from diabetes onset was not sufficient to entirely escape early diabetic complications after mean 13 years of diabetes duration, even if the prevalence of retinopathy and especially nephropathy was lower than usually reported. The clinical picture at onset of diabetes was unchanged the last 25 years. There was no secular trend of partial diabetes remission or C-peptide secretion during the first years after diagnosis.

Place, publisher, year, edition, pages
Institutionen för molekylär och klinisk medicin , 2006.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 945
Keyword [en]
Diabetes mellitus type 1, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, epidemiology, C-peptide
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-6377ISBN: 91-85497-82-7 (print)OAI: oai:DiVA.org:liu-6377DiVA: diva2:21788
Public defence
2006-05-24, K1, Kåkenhus, Campus Norrköping, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2006-05-03 Created: 2006-05-03 Last updated: 2009-08-22
List of papers
1. Declining incidence of severe retinopathy in an unselected population of Type 1 diabetes: the Linköping Diabetes Complications Study
Open this publication in new window or tab >>Declining incidence of severe retinopathy in an unselected population of Type 1 diabetes: the Linköping Diabetes Complications Study
2004 (English)In: Diabetologia, ISSN 0012-186X, Vol. 47, no 7, 1266-1272 p.Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis: In a previous study conducted over the last decades we found a decreased incidence of nephropathy but unchanged incidence of severe retinopathy among patients with Type 1 diabetes diagnosed in childhood and with 20 years duration of diabetes. The aim of our current study was to investigate the incidence 5 to10 years later in the same population.

Methods: We studied all 269 patients in whom Type 1 diabetes was diagnosed in childhood between 1961 and 1985 in a district in southeastern Sweden. Ninety-one percent were monitored for retinopathy until at least 1997 and 95% were monitored for nephropathy. Severe retinopathy was defined as laser-treated retinopathy and nephropathy as persistent proteinuria. Survival analysis was used and the patients divided into five cohorts according to the time of onset of diabetes.

Results: The cumulative proportion of severe retinopathy had declined (p=0.006). After 25 years it was 47% (95% CI 34–61), 28% (15–40) and 24% (12–36) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years it was 53% (40–66) and 44% (28–59) in the oldest cohorts. The cumulative proportion of nephropathy after 25 years duration was 30% (18–42), 8% (1–16) and 13% (4–23) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years, it was 32% (20–44) and 11% (2–20) for the oldest cohorts (p<0.0001).

Conclusions/interpretation: In an unselected population with Type 1 diabetes diagnosed in childhood, modern diabetes care markedly reduced the incidence of severe retinopathy and nephropathy.

Keyword
Diabetic nephropathy, Diabetic retinopathy, Incidence, Population, Type 1 diabetes mellitus
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13829 (URN)10.1007/s00125-004-1431-6 (DOI)
Available from: 2006-05-03 Created: 2006-05-03 Last updated: 2009-08-20
2. Early diabetic complications in a population of young patients with Type 1 diabetes mellitus despite intensive treatment
Open this publication in new window or tab >>Early diabetic complications in a population of young patients with Type 1 diabetes mellitus despite intensive treatment
2006 (English)In: Journal of Pediatric Endocrinology & Metabolism, ISSN 0334-018X, Vol. 19, no 1, 45-54 p.Article in journal (Refereed) Published
Abstract [en]

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.

Keyword
type 1 diabetes mellitus ; diabetic nephropathy ; diabetic neuropathy ; diabetic retinopathy ; prevalence
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13830 (URN)16509528 (PubMedID)
Available from: 2006-05-03 Created: 2006-05-03 Last updated: 2014-09-01Bibliographically approved
3. Clinical manifestations and beta cell function in Swedish diabetic children have remained unchanged during the last 25 years
Open this publication in new window or tab >>Clinical manifestations and beta cell function in Swedish diabetic children have remained unchanged during the last 25 years
2008 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 24, no 6, 472-479 p.Article in journal (Refereed) Published
Abstract [en]

Background: The incidence of type 1 diabetes in childhood has doubled in Sweden during the last decades. Environmental factors may cause a different disease process, residual beta cell function and clinical manifestation. Insulin therapy has become more intensive. The aim of this study was to examine the clinical characteristics at onset C-peptide secretion during the first years, after diagnosis and if there was any secular trends during the last 25 years.

Methods: All 316 children diagnosed with type 1 diabetes during 1976-2000 and living in the Linkoping area were included. Information about clinical characteristics at diagnosis, duration of partial remission, insulin therapy at diagnosis and during the first years was collected from medical records. C-peptide secretion (fasting and stimulated) was measured regularly during the first 5 years. For analysis, the population was divided in five cohorts according to the year of diagnosis.

Results: The clinical characteristics at onset were unchanged as well as duration of partial remission. C-peptide secretion was highest after 3 months and then declined gradually. After 5 years 32.7% of the patients had measurable fasting C-peptide, but only 6.5% >0.1 nmol/L. HbA(1c) and insulin doses were lower in patients with persistent fasting C-peptide secretion >0.1 nmol/L. The cohort 1996-2000 had higher stimulated C-peptide secretion at diagnosis and at 3 months, after longer follow-up there was no difference.

Conclusion: The clinical characteristics at diagnosis, partial remission and duration of C-peptide secretion have remained largely unchanged for the last 25 years.

 

Keyword
diabetes mellitus, type 1, C-peptide, metabolic control, partial remission, children
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16085 (URN)10.1002/dmrr.871 (DOI)
Available from: 2009-01-07 Created: 2009-01-07 Last updated: 2017-12-14
4. Good glycemic control remains crucial in prevention of late diabetic complications - the Linkoping Diabetes Complications Study
Open this publication in new window or tab >>Good glycemic control remains crucial in prevention of late diabetic complications - the Linkoping Diabetes Complications Study
2009 (English)In: PEDIATRIC DIABETES, ISSN 1399-543X, Vol. 10, no 3, 168-176 p.Article in journal (Refereed) Published
Abstract [en]

Several intervention studies have convincingly demonstrated the importance of good glycemic control to avoid long-term diabetic complications, but the importance of other risk factors remains controversial. We previously reported a markedly reduced incidence of severe retinopathy and nephropathy during the past decades in an unselected population of type 1 diabetes mellitus diagnosed in childhood. The aim of the present study was to analyze possible risk factors, which could explain the improved prognosis.

In this longitudinal population-based cohort study, we followed all 269 patients in whom type 1 diabetes mellitus was diagnosed in childhood 1961-1985 in a well-defined geographical area in Sweden. The patients were followed until the end of 1990s. Multivariable regression models were used to analyze the importance of hemoglobin A1c (HbA(1c)), diabetes duration, blood pressure, cardiovascular risk factors and persisting C-peptide secretion for the development of diabetic retinopathy and nephropathy.

Beside longer duration and higher HbA(1c), blood pressure and lipid values were higher and cardiovascular disease and smoking were more common in patients with severe complications. However, multivariable analysis abolished these associations. Diabetes duration and long-term HbA(1c) were the only significant independent risk factors for both retinopathy and nephropathy. The risk of overt nephropathy increased substantially when HbA(1c) was above 9.6% [Diabetes Control and Complications Trial (DCCT) corrected value], while the risk of severe retinopathy increased already when HbA(1c) exceeded 8.6%.

In this unselected population, glycemic control was the only significant risk factor for the development of long-term complications.

Keyword
blood pressure, C-peptide, diabetic nephropathy, diabetic retinopathy, glycosylated, hemoglobin A
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18141 (URN)10.1111/j.1399-5448.2008.00472.x (DOI)
Available from: 2009-05-09 Created: 2009-05-08 Last updated: 2009-08-20

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Nordwall, Maria

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