Background: Advanced glycation end products (AGEs) are long-lived tissue proteins that accumulate in diabetes. Skin AGEs measured in biopsy specimens strongly correlated with complications of diabetes. AGEs can also be measured noninvasively by the AGE Reader™ (DiagnOptics B.V., Groningen, The Netherlands). The aim of this review was to systematically review all articles on the association between skin autofluorescence (SAF), measured by the AGE Reader, and complications of diabetes. Methods: We screened PubMed for studies on SAF and complications in diabetes mellitus type 1 and type 2. Seven articles met the inclusion criteria. Results: All studies showed positive associations of SAF with one or more complications (all-cause mortality, cardiovascular mortality, micro- and macrovascular complications, neuropathy, and nephropathy), except retinopathy. Only three studies were of prospective design, with a follow-up of 3–5 years; the other four studies were cross-sectional. Studies were of large clinical heterogeneity. Conclusions: This systematic review of literature showed an association of SAF with end-organ complications in diabetes, except retinopathy, in all seven studies. However, studies were of large clinical heterogeneity, only three studies had a prospective design, and five studies were from the same research group. More prospective studies, with a longer period of follow-up, larger group size, and strict definitions of complications and end points, are needed to demonstrate the potential role and benefit in clinical management before the widespread use of the AGE Reader can be recommended.

Background: In phenylketonuria (PKU), elevated blood phenylalanine (Phe) concentrations are considered to impair transport of large neutral amino acids (LNAAs) from blood to brain. This impairment is believed to underlie cognitive deficits in PKU via different mechanisms, including reduced cerebral protein synthesis. In this study, we investigated the hypothesis that impaired LNAA influx relates to reduced cerebral protein synthesis.Methods: Using positron emission tomography, L-[1-¹¹C]-tyrosine (¹¹C-Tyr) brain influx and incorporation into cerebral protein were studied in 16 PKU patients (median age 24, range 16 – 47 years), most of whom were early and continuously treated. Data were analyzed by regression analyses, using either¹¹C-Tyr brain influx or¹¹C-Tyr cerebral protein incorporation as outcome variable. Predictor variables were baseline plasma Phe concentration, Phe tolerance, age, and¹¹C-Tyr brain efflux. For the modelling of cerebral protein incorporation,¹¹C-Tyr brain influx was added as a predictor variable.Results: ¹¹C-Tyr brain influx was inversely associated with plasma Phe concentrations (median 512, range 233 – 1362 μmol/L; delta adjusted R²=0.571, p=0.013). In addition,¹¹C-Tyr brain influx was positively associated with¹¹C-Tyr brain efflux (delta adjusted R²=0.098, p=0.041). Cerebral protein incorporation was positively associated with¹¹C-Tyr brain influx (adjusted R²=0.567, p<0.001). All additional associations between predictor and outcome variables were statistically nonsignificant.Conclusions: Our data favour the hypothesis that an elevated concentration of Phe in blood reduces cerebral protein synthesis by impairing LNAA transport from blood to brain. Considering the importance of cerebral protein synthesis for adequate brain development and functioning, our results support the notion that PKU treatment be continued in adulthood. Future studies investigating the effects of impaired LNAA transport on cerebral protein synthesis in more detail are indicated.

Assess prevalence of hepatic steatosis (HS) and of fibrosis in an unselected population of patients with type 1 diabetes. Describe their clinical profile and explore the association between insulin resistance and NAFLD as secondary objectives. We prospectively assessed NAFLD by transient elastography in adult outpatients with type 1 diabetes. Patients were eligible if they did not have any known secondary cause of liver disease. NAFLD was defined as HS with or without fibrosis/cirrhosis. Associations between estimated glucose disposal rate (eGDR) and metabolic syndrome, as surrogate markers of insulin resistance, and NAFLD were explored using multivariate logistic regression models, adjusting for age, sex and diabetes duration. We enrolled 150 consecutive subjects (age 47 ± 14 years, male 55%, diabetes duration 25 ± 14 years, median BMI 25 kg/m²). NAFLD prevalence was 20% (n = 30). Thirty patients (20%) had HS. Five patients (3.3%) had HS with fibrosis. eGDR and metabolic syndrome were statistically significantly associated with the presence of NAFLD (OR 0.62, 95% CI 0.49-0.77, OR 7.62, 95% CI 2.95-19.77). NAFLD prevalence in patients with type 1 diabetes is considerable, mainly restricted to isolated HS, while fibrosis is rare. Insulin resistance is associated with NAFLD in patients with type 1 diabetes.

The objective was to describe pre-gestational history and the maternal, fetal and neonatal outcome in pregnancies in women with pre-gestational type 2 diabetes during the period between 1992 and 2006 from one center in the Netherlands. Patients attending the obstetric-diabetology outpatient clinic of a tertiary referral center were studied. This center also has a regular diabetes clinic and a community midwifery service. Patients were identified from the database. Maternal outcome (pre-eclampsia, pre-term delivery, Caesarean section) and fetal and neonatal outcome (macrosomia, congenital malformations, perinatal mortality, neonatal hypoglycemia) were analyzed as well HbA1c levels, planning of pregnancy, gestational age at first antenatal visit and ethnic background. Sixty-six singleton pregnancies from 48 women were analyzed. Their age was 34 +/- 5 yr, the BMI 31.7 +/- 7.4 and the median duration of diabetes was 3 yr. 52% were Caucasian and 35% were of Moroccan descent. 49% did not complete secondary school. Moroccan descent was associated with a lower educational level and a BMI comparable with the whole study group. The proportion of planned pregnancies was approximately 70%. The mean HbA1c in the first trimester was 6.4 +/- 1.1% and the gestational age at first visit was 10 +/- 5 wk, in one-quarter before 6 wk. The prevalences of variables related to maternal and neonatal outcome were as follows: spontaneous abortion 13.6%, pre-eclampsia 8.9%, pre-term delivery 21.4%, spontaneous labor 25.0%, induced labor 48.2%, Caesarean section 42.9%, macrosomia (>/=90th percentile) 41.1%, severe hypoglycemia 41.5% and major congenital malformations 5.1%. Pre-gestational type 2 diabetes is associated with an increased incidence of adverse pregnancy outcome despite reasonable mean HbA1c level and despite a high frequency of planned pregnancies. Many women report relatively late. Improvement in the outcome requires more active peri-gestational specialist care and a tailored approach is required towards migrant communities.

Background: Type 2 diabetes is associated with considerable comorbidity and severe complications, which reduce quality of life of the patients and require high levels of healthcare. The Diabetes Pearl is a large cohort of patients diagnosed with type 2 diabetes, covering different geographical areas in the Netherlands. The aim of the study is to create a research infrastructure that will allow the study of risk factors, including biomarkers and genetic determinants for severe diabetes complications. Methods/design: Baseline examinations began November 2009 and will continue through 2012. By the end of 2012, it is expected that 7000 patients with type 2 diabetes will be included in the Diabetes Pearl cohort. To ensure quality of the data collected, standard operation procedures were developed and used in all 8 recruitment centers. From all patients who provide informed consent, the following information is collected: personal information, medication use, physical examination (antropometry, blood pressure, electrocardiography (ECG), retina photographs, ankle-brachial index, peripheral vibration perception), self-report questionnaire (socio-economic status, lifestyle, (family) history of disease, and psychosocial well-being), laboratory measurements (glucose, A1c, lipid profile, kidney function), biobank material (storage of urine and blood samples and isolated DNA). All gathered clinical data and biobank information is uploaded to a database for storage on a national level. Biobanks are maintained locally at all recruitment centers. Discussion: The Diabetes Pearl is large-scale cohort of type 2 diabetes patients in the Netherlands aiming to study risk factors, including biomarkers and genetic markers, for disease deterioration and the development of severe diabetes complications. As a result of the well-designed research design and the national coverage, the Diabetes Pearl data can be of great value to national and international researchers with an interest in diabetes related research.