Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden.

OBJECTIVE: To investigate the relationship between early-onset retinopathy and urinary markers of renal dysfunction. RESEARCH DESIGN AND METHODS: The Diabetes Incidence Study in Sweden (DISS) aims to register all new cases of diabetes in young adults (15-34 years). In 1987-1988, 806 patients were reported and later invited to participate in a follow-up study focusing on microvascular complications after approximately 10 years of diabetes. In the present study, 149 patients with type 1 diabetes, completed eye examination, and urine sampling were included. RESULTS: The patients with retinopathy (n=58, 39%) had higher HbA(1c) (P<.001) and urinary IgG2/creatinine (P<.05) and IgG2/IgG4 ratios (P<.05). Patients with maculopathy had the highest levels. No significant differences in urinary albumin/creatinine, glycosaminoglycans (GAGs)/creatinine, Tamm-Horsfall protein (THP)/creatinine, and IgG4/creatinine ratios were found. Women had higher urinary albumin/creatinine (P<.01) and urinary IgG2/creatinine ratios (P<.01) than men. CONCLUSIONS: Young adults with type 1 diabetes and early-onset retinopathy had higher IgG2/creatinine and IgG2/IgG4 ratios than patients without retinopathy indicating that retinopathy is associated with a change in glomerular size selectivity. This was found in association with normal urinary albumin and THP excretion and may be suspected to reflect early general vascular changes.

Assessment of toe blood pressure is an effective screening method to identify diabetes patients with lower extremity arterial disease.

The authors evaluated a screening program for lower extremity arterial disease (LEAD) in diabetic patients and focused on the value of toe blood pressure assessment. They recruited 437 subjects, ages 30-70 years (134 healthy controls, 166 type 1 and 137 type 2 diabetic patients; control [Ctr], DM1, and DM2) with no previous history of LEAD. They were enrolled in a longitudinal study with a planned follow-up of 10 years. Patients were consecutively enrolled from outpatient diabetes units of 2 university hospitals. Subjects were screened with respect to peripheral circulation by use of established noninvasive techniques. These included arm, ankle (AP), and toe (TP) blood pressure measurements; evaluation of peripheral neuropathy; and a standardized physical examination. Results from the baseline examination are presented in this report. The number of patients who presented peripheral pressures or indices below normal (< mean -2 SD for controls) was higher among diabetic patients; 24% of DM1 and 31% of DM2, as compared to 6% of Ctr, had at least 1 lower limb with a low TP, AP, toe/arm index (TI), or ankle/arm index (AI), and these subjects were mainly identified by using the toe/arm index. TI was independently and negatively associated with fasting blood glucose in both patient groups, and with smoking, age, and diabetes duration in DM1. The mean AP was higher in the DM1 and DM2 groups compared to Ctr, whereas overall TP, TI, and AI were similar in the groups. It was also shown that abnormally low TI was significantly more common than low AI among diabetics (p<0.001), and this was true for TP vs AP as well (p<0.05). It is beneficial to include assessment of toe blood pressure and toe/arm blood pressure index to detect early LEAD in diabetic patients. Ankle blood pressure and indices alone are less efficient, owing probably to medial sclerosis in diabetic patients. Up to 30% of diabetic patients with no ischemic symptoms may have signs of impaired arterial circulation.

Gastrointestinal symptoms in type 1 diabetic patients, as compared to a general population. A questionnaire-based study.

OBJECTIVES: To examine the prevalence of gastrointestinal (GI) symptoms in patients with type 1 diabetes as compared to age- and sex-matched controls. METHOD: 395 patients with type 1 diabetes, registered at the diabetes outpatient unit at the Sahlgrenska University Hospital, were studied by use of a GI symptom questionnaire. They were randomly selected within 10-year age intervals from 20 to 69 years. Age- and sex-matched controls (n=242) were sampled from a cohort recruited from the general population. RESULTS: While the study populations were well matched with regard to age, sex and body mass index (BMI), the diabetic population comprised more smokers and reported symptoms of respiratory and ischemic heart disease more frequently. Symptoms of heartburn, acid regurgitation, nausea and vomiting were significantly more frequent and intense in the diabetic cohort. The occurrence of GI symptoms co-varied with the presence of respiratory and cardiac symptoms but was not predicted by age, glycosylated haemoglobin (HbA1c) levels or the presence of peripheral neuropathy. CONCLUSION: Patients with diabetes type 1 had more frequent and intense upper and lower GI symptoms than age- and sex-matched controls, especially if only moderate and severe symptoms were considered. The presence of symptoms was related to lifestyle factors but not to the degree of diabetes control as expressed by the level of HbA1c and the presence of peripheral neuropathy.

Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).

OBJECTIVE: To estimate the occurrence of early-onset renal involvement in a nationwide population-based cohort of young adults with diabetes in Sweden and relate the findings to glycemic control, type of diabetes, sex, smoking, and blood pressure. RESEARCH DESIGN AND METHODS: The Diabetes Incidence Study in Sweden aims to register all incident cases of diabetes in the age-group 15-34 years. In 1987-1988, 806 patients were reported and invited to participate in a follow-up study focusing on microvascular complications. Of them, 469 subjects participated. The assessment was based on questionnaires (n = 469), blood samples (n = 424), urine samples (n = 251) and, when appropriate, medical records (n = 186). RESULTS: During the follow-up time, median 9 years (range 6-12), 31 of 469 patients (6.6%) with incipient or overt diabetic nephropathy (i.e., micro- or macroalbuminuria) were found, 24 of 426 (5.6%) in type 1 and 7 of 43 (16%) in type 2 diabetic subjects (P = 0.016). Additionally, 24 of 31 patients (77%) had microalbuminuria and 7 (23%) had macroalbuminuria, which mainly occurred in patients with type 2 diabetes. In a Cox regression analysis, high mean HbA(1c) during the follow-up period and high blood pressure at follow-up increased the risk of developing signs of nephropathy (P = 0.020 and P = 0.003, respectively). Compared with patients with type 1 diabetes, those with type 2 diabetes tended to have an increased risk of renal involvement (P = 0.054) when adjusting for sex, tobacco use, glycemic control, and blood pressure. CONCLUSIONS: Despite modern treatment and self-monitoring of blood glucose, young adult patients with diabetes may still develop renal involvement during the first 10 years of diabetes duration. Inadequate HbA(1c), high blood pressure, and type 2 diabetes appear to be risk markers for early occurrence of diabetic nephropathy.

The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).

OBJECTIVE: To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden. RESEARCH DESIGN AND METHODS: The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15-34 years in Sweden. In 1987-1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8-10 years later. The assessment was based on retinal photographs in most cases (86%). RESULTS: Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA(1c) 8.1 +/- 1.5% and 6.8 +/- 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA(1c) (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001). CONCLUSIONS: Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.

Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.

Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.