Maria Nordwall

Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes— the Linköping Diabetes Complications Study

Aims/hypothesisIn 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.MethodsWe 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.ResultsThe 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/interpretationIn an unselected population with Type 1 diabetes diagnosed in childhood, modern diabetes care markedly reduced the incidence of severe retinopathy and nephropathy.

Lyme Neuroborreliosis in Children - a Prospective Study of Clinical features, Prognosis, and Outcome

Background: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery. Material/Methods: Children being evaluated for NB (n = 177) in southeast Sweden were categorized into 3 groups: “confirmed neuroborreliosis” (41%) with Borrelia antibodies in the cerebrospinal fluid, “possible neuroborreliosis” (26%) with pleocytosis but no Borrelia antibodies in the cerebrospinal fluid, and “not determined” (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid. Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174). Results: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified. Conclusions: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.

Good glycemic control remains crucial in prevention of late diabetic complications – the Linköping Diabetes Complications Study

Background:  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.

Impact of HbA1c, Followed From Onset of Type 1 Diabetes, on the Development of Severe Retinopathy and Nephropathy: The VISS Study (Vascular Diabetic Complications in Southeast Sweden)

OBJECTIVE HbA1c is strongly related to the development of diabetes complications, but it is still controversial which HbA1c level to strive for in the treatment of type 1 diabetes. The aim of the current study was to evaluate HbA1c, followed from diagnosis, as a predictor of severe microvascular complications and to formulate HbA1c target levels for treatment. RESEARCH DESIGN AND METHODS A longitudinal observation study followed an unselected population of 451 patients diagnosed with type 1 diabetes during 1983–1987 before the age of 35 years in a region of Southeast Sweden. Retinopathy was evaluated by fundus photography and nephropathy data collected from medical records. HbA1c was measured starting from diagnosis and during the whole follow-up period of 20–24 years. Long-term weighted mean HbA1c was then calculated. Complications were analyzed in relation to HbA1c levels. RESULTS The incidence of proliferative retinopathy and persistent macroalbuminuria increased sharply and occurred earlier with increasing long-term mean HbA1c. None of the 451 patients developed proliferative retinopathy or persistent macroalbuminuria below long-term weighted mean HbA1c 7.6% (60 mmol/mol); 51% of the patients with long-term mean HbA1c above 9.5% (80 mmol/mol) developed proliferative retinopathy and 23% persistent macroalbuminuria. CONCLUSIONS Long-term weighted mean HbA1c, measured from diagnosis, is closely associated with the development of severe complications in type 1 diabetes. Keeping HbA1c below 7.6% (60 mmol/mol) as a treatment target seems to prevent proliferative retinopathy and persistent macroalbuminuria for up to 20 years.

Age-dependent decline of β-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study.

C‐peptide secretion is currently the only available clinical biomarker to measure residual β‐cell function in type 1 diabetes. However, the natural history of C‐peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C‐peptide decline over time from type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c) levels and insulin dose.

Long-term Clinical Outcome After Lyme Neuroborreliosis in Childhood

OBJECTIVES: To determine long-term clinical outcome in children with confirmed Lyme neuroborreliosis (LNB) and to evaluate persistent subjective symptoms compared with a control group. METHODS: After a median of 5 years, 84 children with confirmed LNB underwent a neurologic re-examination, including a questionnaire. Medical records were analyzed, and a control group (n = 84) was included. RESULTS: The total recovery rate was 73% (n = 61). Objective neurologic findings, defined as “definite sequelae,” were found in 16 patients (19%). The majority of these children had persistent facial nerve palsy (n = 11), but other motor or sensory deficits occurred (n = 5). Neurologic signs and/or symptoms defined as “possible sequelae” were found in another 7 patients (8%), mainly of sensory character. Nonspecific subjective symptoms were reported by 35 patients (42%) and 32 controls (38%) (nonsignificant). Affected daily activities or school performance were reported to the same extent in both groups (23% vs 20%, nonsignificant). CONCLUSIONS: The long-term clinical recovery rate was 73% in children with confirmed LNB. Persistent facial nerve palsy occurred in 13%, whereas other motor or sensory deficits were found in another 14%. Neurologic deficits did not affect daily activities or school performance more often among patients than controls and should be considered as mild. Furthermore, nonspecific subjective symptoms such as headache, fatigue, or memory or concentration problems were reported as often among patients as controls and should not be considered as sequelae after LNB.

Parents of Adolescents with Type 1 Diabetes - Their Views on Information and Communication Needs and Internet Use. A Qualitative Study

Background Little is known about parents’ views on the use of online resources for information, education and support regarding childhood type 1 diabetes (T1DM). Considering the rapidly evolving new communication practices, parents’ perspectives need to be explored. The main purpose of this paper was to explore parents’ perceptions of their information-seeking, Internet use, and social networking online. This applied to their everyday life, including the contexts of T1DM and contact with peers. A second aim was to identify implications for future development of Internet use in this respect. Methodology/Principal Findings Twenty-seven parents of 24 young persons aged 10–17 with T1DM participated in eight focus group interviews during their regular visits to a county hospital. Focus group discussions were video/audio-taped, transcribed and analysed using inductive qualitative content analysis. Self-reported demographic and medical information was also collected. A main theme was Finding things out, including two sub-themes, Trust and Suitability. The latter were key factors affecting parents’ perceptions of online resources. Parents’ choice of information source was related to the situation, previous experiences and knowledge about sources and, most importantly, the level of trust in the source. A constantly present background theme was Life situation, including two sub-themes, Roles and functions and Emotions and needs. Parents’ information-seeking regarding T1DM varied greatly, and was closely associated with their life situation, the adolescents development phases and the disease trajectory. Conclusions/Significance Health practitioners and system developers need to focus on creating trust and suitability for users’ needs. They should understand the children’s diverse needs, which depend on their life situation, on the children’s development, and on the disease trajectory. To enhance trust in online health information and support services, the participation of local practitioners is crucial.

Clinical manifestations and beta cell function in Swedish diabetic children have remained unchanged during the last 25 years.

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.

Early diabetic complications in a population of young patients with type 1 diabetes mellitus despite intensive treatment.

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 > or = 2 of 4 nerves (sural and peroneal nerves), nephropathy as albumin excretion rate > or = 20 microg/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.

BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children

OBJECTIVE Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. DESIGN Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. METHODS Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (<5 years, n=126; >5 years <10 years, n=295; >10 years <18 years, n=421; >18 years, n=410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. RESULTS In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed >18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (β 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2) higher baseline BMI (P=0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (β=0.026, 95% CI=0.0097, 0.042; P=0.002). CONCLUSIONS These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of β-cell function in type 1 diabetes.