Short adult stature has previously been associated with cardiovascular disease, but its relationship with the microvascular complications of diabetes is uncertain. Therefore, we evaluated the association between adult stature and prevalence and incidence of diabetic microvascular complications.
This cross-sectional and longitudinal study comprises 3,968 adult patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and 1,246 adult patients from the Diabetes Control and Complications Trial (DCCT). In FinnDiane, diabetic nephropathy was defined as urinary albumin excretion > or = 300 mg/24 h, dialysis, or renal transplantation. Retinopathy was divided into background and proliferative (laser-treated) retinopathy. In the DCCT, original nephropathy (class 1-6) and retinopathy (Early Treatment of Diabetic Retinopathy Study) classifications were used.
In the FinnDiane study, patients in the lowest quartile of adult height had increased risks of prevalent diabetic nephropathy (odds ratio [OR] 1.71, 95% CI 1.44-2.02) and prevalent laser-treated retinopathy (1.66, 1.43-1.93) compared with other patients. Similarly, in the DCCT, patients in the lowest quartile of adult height had increased risks of incident diabetic nephropathy class 4-6 (hazard ratio 2.70, 95% CI 1.59-4.59) and incident proliferative retinopathy (2.06, 1.15-3.71). In the FinnDiane study, the associations were largely explained by childhood exposure to diabetes. However, in the DCCT, where a greater proportion of patients had diabetes onset >18 years, the association with nephropathy was independent of childhood diabetes exposure.
Short adult stature is associated with microvascular complications in patients with type 1 diabetes. These findings are compatible with either childhood diabetes exposure or "common soil" or both as potential explanations.
To examine the association between neurodevelopmental problems and high HbA1c among paediatric patients with type 1 diabetes.
A population-based study was performed among patients with type 1 diabetes (5-16 years) in two Swedish counties (n = 233). The Five to Fifteen (FTF) questionnaire targeted neurodevelopmental qualities. Scores above the 90th percentile in the various domains are considered as definitive problems and scores above the 75th percentile as mild. FTF scores were compared with regard to HbA1c =73 mmol/mol and >73 mmol/mol (8.0%).
The response rate was 190 (82%). Neurodevelopmental problems were not overrepresented among patients in general. Memory and learning problems were associated with HbA1c >73 mmol/mol (p = 0.01). This correlation was especially seen in adolescents (12-16 years) where mild executive problems (adjOR 3.1), definite memory problems (adjOR 5.0) and definite learning problems (adjOR 5.0) were associated with HbA1c >73 mmol/mol after adjustment for gender, diabetes duration and age of onset.
Our findings that high HbA1c is more common in adolescent diabetes patients with neurodevelopmental problems generate the hypothesis that these problems might precede poor metabolic control. If so, early detection of neurodevelopmental problems would allow individually tailored treatment that may improve metabolic control and prevent complications.
OBJECTIVE: The aim of this work was to study the impact of glycemic control (HbA(1c)) early in disease and age at onset on the occurrence of incipient diabetic nephropathy (MA) and background retinopathy (RP) in childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: All children, diagnosed at 0-14 years in a geographically defined area in northern Sweden between 1981 and 1992, were identified using the Swedish Childhood Diabetes Registry. From 1981, a nationwide childhood diabetes care program was implemented recommending intensified insulin treatment. HbA(1c) and urinary albumin excretion were analyzed, and fundus photography was performed regularly. Retrospective data on all 94 patients were retrieved from medical records and laboratory reports. RESULTS: During the follow-up period, with a mean duration of 12 +/- 4 years (range 5-19), 17 patients (18%) developed MA, 45 patients (48%) developed RP, and 52% had either or both complications. A Cox proportional hazard regression, modeling duration to occurrence of MA or RP, showed that glycemic control (reflected by mean HbA(1c)) during the follow-up was significantly associated with both MA and RP when adjusted for sex, birth weight, age at onset, and tobacco use as potential confounders. Mean HbA(1c) during the first 5 years of diabetes was a near-significant determinant for development of MA (hazard ratio 1.41, P = 0.083) and a significant determinant of RP (1.32, P = 0.036). The age at onset of diabetes significantly influenced the risk of developing RP (1.11, P = 0.021). Thus, in a Kaplan-Meier analysis, onset of diabetes before the age of 5 years, compared with the age-groups 5-11 and >11 years, showed a longer time to occurrence of RP (P = 0.015), but no clear tendency was seen for MA, perhaps due to lower statistical power. CONCLUSIONS: Despite modern insulin treatment, >50% of patients with childhood-onset type 1 diabetes developed detectable diabetes complications after approximately 12 years of diabetes. Inadequate glycemic control, also during the first 5 years of diabetes, seems to accelerate time to occurrence, whereas a young age at onset of diabetes seems to prolong the time to development of microvascular complications.
Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, FinlandDepartment of Ophthalmology, Helsinki University Central Hospital, Helsinki, FinlandDivision of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, FinlandThe Baker IDI Heart and Diabetes Institute, Melbourne, Vic., Australia.
To investigate whether age at onset of type 1 diabetes is a risk factor for clinically significant macular oedema (CSME).
A sample of 1354 patients with a mean duration of diabetes 24.6 ± 11.6 years was drawn from the FinnDiane Study population and divided into age at onset groups 0-4 (n = 184), 5-14 (n = 662) and 15-40 years (n = 508). Type 1 diabetes was defined as age at onset =40 years, C-peptide negativity and insulin treatment initiated within 1 year of diagnosis. Retinopathy status was assessed from fundus photographs and stereoscopic fundus examinations and graded with the ETDRS scale.
After 30 years of diabetes, the estimated cumulative incidences of CSME were 17% (95% CI 11-26) in age at onset group 0-4 years, 27% (95% CI 23-32) in age at onset group 5-14 years and 34% (95% CI 27-41) in age at onset group 15-40 years (p = 0.002, Gray's test). In a competing risks regression model, adjusted for covariates selected with Bayesian information criteria, age at onset 5-14 years (HR 1.89 [95% CI 1.22-2.91], p = 0.004), and age at onset 15-40 years (HR 3.72 [95% CI 2.35-5.89], p
We studied the incidence of blindness and visual impairment in patients who were enrolled in a photographic control- and screening program for diabetic retinopathy. The study cohort consisted of 2133 patients examined between January 1990 and December 1992 and followed until October 1st 1995. The occurrence of blindness (visual acuity or = 8.5%, were associated with a 65% increase in risk of blindness/visual impairment (95% confidence interval 14-130%). Retinopathy was the major cause of blindness and visual impairment in patients with diabetes. The study revealed a low incidence of blindness, which is in line with recent reports. Control of hyperglycaemia may be of value for the prevention of visual loss.
The influence of glucagon on glycaemic control in type 1 diabetes is debated. We investigated the relationship between postprandial glucagon levels and HbA1c during a period up to 60 months after diagnosis of childhood type 1 diabetes.
The Danish remission phase cohort comprised 129 children (66 boys) with type 1 diabetes whose mean (SD) age at onset was 10.0 (3.9) years. Liquid mixed-meal tests were performed prospectively at 1, 3, 6 and 12 months and a subset of 40 patients completed follow-up at 60 months. Postprandial (90 min) plasma levels of glucagon, glucose (PG), C-peptide, total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and HbA1c were analysed. Multivariate regression (repeated measurements with all five visits included) was applied and results expressed as relative change (95% CI).
Postprandial glucagon levels increased 160% from 1 to 60 months after diagnosis (p
PURPOSE: As a consequence of an increasing prevalence of short-sightedness (myopia) in countries that have adopted western dietary patterns, it has been hypothesized that hyperglycaemia and hyperinsulinaemia induce myopia. The purpose of this study was to evaluate the relation between glycosylated haemoglobin (HbA(1c)), insulin dosage and myopia in diabetic patients. METHODS: All type 1 diabetic patients aged 16-26 years [mean age 22.0, standard deviation (SD) 2.9] attending the eye clinic at Steno Diabetes Center, Copenhagen, in 1995-1997 were included in the study (n = 393). The following data were collected from the medical records from baseline to 2005: age at diabetes onset, age at baseline, sex, weight, HbA(1c), insulin dosage, refractive error, visual acuity and ocular diabetes complications. Results: The prevalence of myopia [spherical equivalent (SE)
Latent autoimmune diabetes in adults (LADA) usually refers to GAD65 autoantibodies (GADAb)-positive diabetes with onset after 35 years of age and no insulin treatment within the first 6 months after diagnosis. However, it is not always easy to distinguish LADA from type 1 or type 2 diabetes. In this study, we examined whether metabolite profiling could help to distinguish LADA (n = 50) from type 1 diabetes (n = 50) and type 2 diabetes (n = 50). Of 123 identified metabolites, 99 differed between the diabetes types. However, no unique metabolite profile could be identified for any of the types. Instead, the metabolome varied along a C-peptide-driven continuum from type 1 diabetes via LADA to type 2 diabetes. LADA was more similar to type 2 diabetes than to type 1 diabetes. In a principal component analysis, LADA patients overlapping with type 1 diabetes progressed faster to insulin therapy than those overlapping with type 2 diabetes. In conclusion, we could not find any unique metabolite profile distinguishing LADA from type 1 and type 2 diabetes. Rather, LADA was metabolically an intermediate of type 1 and type 2 diabetes, with those patients closer to the former showing a faster progression to insulin therapy than those closer to the latter.
To study the frequency of diabetic retinopathy in relation to age at diagnosis, treatment, duration of diabetes and glycemic control as measured by means of HbA1c levels, we performed a cross-sectional, registered-based study in the Helsingborg area of southern Sweden, comprising 2232 diabetic patients. Of the known diabetic population or = 30 years the prevalence of retinopathy was 57% in insulin-treated, and 26% in non-insulin treated patients. Levels of glycated hemoglobin and duration of diabetes were associated with retinopathy in the group with younger onset. In the older-onset group, there was a relationship between retinopathy and duration of diabetes and insulin treatment; glycated hemoglobin had a relationship which was of borderline significance with any retinopathy, but clearly significant with the pooled group: severe non-proliferative, proliferative retinopathy and/or macular edema. Hyperglycemia and duration of diabetes were thus associated with retinopathy in both younger- and older-onset diabetes, but hyperglycemia less so in the older-onset group.