Metabolic Control, Morbidity and Mortality in Type 1 Diabetes with Onset in Childhood/Adolescence

• Aim: The overall aim of this thesis was to study mortality in individuals with onset of type 1 diabetes (T1D) in childhood and adolescence in Sweden, related to clinical characteristics such as metabolic control in childhood/adolescence and comorbidity.  Methods: All studies in this thesis were register-based observational studies using a nationwide and population-based quality register, the paediatric part of the Swe-dish National Diabetes Register (NDR), for identification and collection of clinical data of individuals with T1D diagnosed before 18 years of age. Study I included 8084 individuals between 2000 and 2014, and compared these during follow-up based on HbA1c at onset of T1D. In studies II and IV 16,537 individuals with T1D registered from 2000 to 2014 were identified. This population was merged with the Swedish Cause of Death register (CDR) to identify deceased individuals during the study period and retrieve causes of death. In study II, the study period was set between 2006 and 2014, including 12,652 individuals. Standardised mortality rates (SMRs) were calculated using data from the Swedish population register. Study III included 15,188 individuals with onset of T1D between 2000 and 2019. Five randomly selected control individuals from the Swedish population were matched to each individual with T1D. These cohorts were linked to the National Patient Register to retrieve ICD codes on autoimmune diseases (AIDs), and to the CDR to identify deceased individuals. Medical records were retrieved from treating clinics for all de-ceased individuals in study IV.  Results: Individuals in the highest quintile of HbA1c at onset of T1D (>114 mmol/mol) had higher HbA1c during follow-up compared to the lowest quintile (<72 mmol/mol) at onset, but there was no significant correlation between individual HbA1c at onset and during follow-up. In study II, 68 individuals were identified as deceased, of which almost 40% died due to diabetes, mainly caused by acute complications. The overall SMR was 2.7 per 1000 person-year. Those who died due to diabetes had significantly elevated HbA1c in childhood compared to those who died from other causes or were still alive. In study III, almost 20% of individuals with T1D developed at least one other AID. Coeliac disease was the most common followed by thyroid disease. Individuals with an additional AID did not have worse outcome in terms of metabolic control or mortality risk. In study IV, after review, 72 individuals had information in the medical records which was possible to evaluate regarding cause of death. Hypoglycaemia was the cause of death in two individuals (2.8%) and ketoacidosis in eight individuals (11.1%). In 16 (22.2%) individuals with cause of death due to diabetes with coma, no conclusion on whether death was caused by hypoglycaemia or ketoacidosis could be drawn. HbA1c was significantly elevated both in childhood and in the last year before death in medical records in those deceased due to diabetes.  Conclusions: High HbA1c at onset of T1D cannot be used as a predictor of future metabolic control in the individual child or adolescent. Children and adolescents with high HbA1c in childhood have an increased risk of premature mortality, mainly due to acute complications of T1D. Hypoglycaemia was uncommon as a cause of death, contributing for certain to only 2.8 % of the mortality. Individuals with T1D have a high risk of developing other AIDs from the onset of diabetes; however such comorbidity was not associated with worse outcome in terms of metabolic control or mortality risk. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Type 1 diabetes

HbA1c

Mortality

Autoimmune comorbidity

Publikations- och innehållstyp

vet (ämneskategori)

dok (ämneskategori)