Accumulation of advanced glycation end products is associated with macrovascular events and glycaemic control with microvascular complications in Type 2 diabetes mellitus.

AIM: The United Kingdom Prospective Diabetes Study (UKPDS) study showed that glycaemic control (HbA1c ) can predict vascular complications in Type 2 diabetes mellitus. The Diabetes Control and Complications Trial (DCCT) study showed that accumulation of advanced glycation end products (AGEs) from skin biopsies predicts vascular complications in Type 1 diabetes. Previously, we showed that tissue AGEs can be measured non-invasively using skin autofluorescence (SAF). The aim of this study was to compare the predictive value of HbA1c and SAF for new macrovascular events and microvascular complications in people with Type 2 diabetes. METHODS: A prospective cohort study of 563 participants, median age 64 years [interquartile range (IQR) 57-72], diabetes duration of 13 years, from five Dutch hospitals was performed. RESULTS: After a median follow-up of 5.1 (IQR 4.3-5.9) years, 79 (15%) participants had died and 49 (9%) were lost to follow-up. Some 133 (26%) developed a microvascular complication and 189 (37%) a macrovascular event. Tertiles of HbA1c were significantly associated with development of microvascular complications (log rank P = 0.022), but not with macrovascular events. Tertiles of SAF were significantly associated with macrovascular events (log rank P = 0.003). Cox regression analysis showed SAF was associated with macrovascular events: crude hazard ratio (HR) 1.53 (P < 0.001) per unit increase, HR 1.28 (P = 0.03) after correction for UKPDS score. HbA1c was predictive for microvascular complications: crude HR 1.20 (P = 0.004), HR 1.20 (P = 0.004) after correction for UKPDS score. CONCLUSION: This study shows that tissue accumulation of AGEs, assessed by SAF, is associated with development of macrovascular events in people with Type 2 diabetes, whereas HbA1c is associated with the development of microvascular complications.

Skin autofluorescence and risk of micro- and macrovascular complications in patients with Type 2 diabetes mellitus-a multi-centre study.

AIMS: Skin autofluorescence is a non-invasive marker of advanced glycation end product accumulation. In a previous study, skin autofluorescence correlated with and predicted micro- and macrovascular complications in Type 2 diabetes in a primary care setting. The present cross-sectional study aims to confirm the association between skin autofluorescence and diabetic complications in patients with Type 2 diabetes in a multi-centre secondary care setting. METHODS: We analysed 563 subjects with Type 2 diabetes mellitus from five Dutch hospitals. RESULTS: Median age was 64 years, median duration of diabetes 13 years and median HbA(1c) 58 mmol/mol (7.5%). Sixty-one per cent of patients had microvascular complications (38% nephropathy, 36% retinopathy, 35% neuropathy) and 42% had macrovascular complications. Median UK Prospective Diabetes Study 10-year risk for coronary events was 19%. Median skin autofluorescence was elevated compared with age-matched healthy control subjects: 2.77 (interquartile range 2.39-3.28) vs. 2.46 (2.08-2.84) arbitrary units. Skin autofluorescence was particularly increased in patients with complications: no complications, median 2.56 (2.26-2.90); microvascular complications, 2.79 (2.38-3.29); macrovascular complications, 2.85 (2.41-3.41); both micro- and macrovascular complications, 2.96 (2.56-3.60) arbitrary units, P < 0.001. Logistic regression analysis showed that age, duration of diabetes, renal function, gender, atrial fibrillation and skin autofluorescence were independently associated with macrovascular complications. Multiple regression analysis identified age, smoking, renal function, macrovascular complications and the number of microvascular complications as the determinants of skin autofluorescence. CONCLUSIONS: This study confirms that skin autofluorescence is increased in patients with Type 2 diabetes in a secondary care setting. Skin autofluorescence was associated with macrovascular complications in patients with diabetes and this association was independent of classical risk factors.

[Four patients with incidentalomas of the thyroid discovered on 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET)]. / Vier patiënten met een incidentaloom van de schildklier bij fluor-18-deoxyglucose-positronemissietomografie (FDG-PET).

In 4 patients, an incidentaloma of the thyroid was found on 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET). In the first patient, a 73-year-old man, a medullary thyroid carcinoma was discovered during the staging procedure ofa laryngeal carcinoma. In the second patient, an 81-year-old woman, a follicular thyroid carcinoma was found as a result of a FDG-PET evaluation of an adenocarcinoma of the lung. In the third patient, a 64-year-old woman, a papillary thyroid carcinoma was found during dissemination investigation after curative removal of an adrenocortical carcinoma. The last patient, a 78-year-old man, was found to have a thyroid incidentaloma on FDG-PET scan during staging ofa recurrence of a gastrointestinal stromal tumour. Thyroid incidentalomas are present on 1.2-2.3% of FDG-PET scans. Further diagnostic work-up of these lesions by fine needle aspiration is warranted since up to 50% are malignant. However, whether these malignant thyroid lesions are relevant is not always clear. Treatment depends on the primary disease for which the FDG-PET scan was initially made. This requires good evaluation and discussion with the patient.

[Pituitary apoplexy: an endocrinologic emergency]. / Apoplexie van de hypofyse: een endocrinologisch spoedgeval.

A 32-year-old woman, a 73-year-old man and a 26-year-old pregnant woman presented with headache, vomiting, and variable presence of visual disturbances, impaired consciousness, and circulatory shock. All three had pituitary apoplexy. In the first patient lymphocytic hypophysitis was diagnosed, the second had a nonfunctional adenoma and the last patient probably also. All three patients were treated conservatively with full recovery of signs and symptoms. However pituitary insufficiency remained in all three. Pituitary apoplexy is an acute event with significant morbidity and mortality. The cause is a rapid expansion of, usually, a pre-existing, often not yet known, adenoma by massive haemorrhage or infarction. Pressure, among other things, causes hypopituitarism, meningism, compression of the chiasma opticum and visual disturbances. Although many predisposing factors have been identified, pituitary apoplexy is often an unpredictable event. Diagnosis is made by the typical clinical presentation, eye examination, MRI and by measuring pituitary hormones. Treatment is with suppletion of the deficient hormones and in selected patients by transsphenoidal decompression surgery.

[Rupture of thoracic aneurysm in a 10-year old boy]. / Ruptuur van een thoracaal aneurysma bij een 10-jarige jongen.

A 10-year-old boy with a medical history of fatigue became nauseous, short of breath and cyanotic within 24 hours after a frightening incident. He was successfully resuscitated after a cardiac arrest. A CT scan revealed a ruptured aneurysm of the ascending aorta. During emergency surgery the ascending aorta and aortic arch were replaced with a 22 mm synthetic graft. No postoperative complications occurred. There was no associated trauma, syphilis, collagen diseases (Marfan's syndrome, Ehlers-Danlos syndrome), congenital heart disease or autoimmune disease. The cause of the aneurysm and rupture remain unclear.

Skin autofluorescence and glycemic variability.

BACKGROUND: Accumulation of advanced glycation end products (AGEs) is accelerated during glycemic and oxidative stress and is an important predictor of complications in diabetes mellitus (DM). STUDY DESIGN: Here we both review and present original data on the relationship between skin autofluorescence (SAF), a noninvasive measure of AGEs, and short- and intermediate-term glycemic variations. RESULTS: Acute changes in glucose levels during an oral glucose tolerance test in 56 persons with varying degrees of glucose tolerance did not influence SAF. AGE-rich meals result in a transient postprandial rise in SAF of 10% 2-4 h later. This could not be attributed to meal-induced glycemic changes and is probably caused by the AGE content of the meal. In type 1 DM major intermediate-term improvements of glycemic control as depicted by multiple hemoglobin A1c (HbA1c) measurements were associated with lower skin AGE levels. In a well-controlled, stable type 2 DM cohort, only a weak correlation was found between SAF and HbA1c. In both studies skin AGE/SAF levels predicted complications of diabetes with an accuracy superior to that of HbA1c. SAF has also been proposed as a new tool in diagnosing impaired glucose tolerance (IGT) and DM. It proved to be more sensitive than either fasting glucose or HbA1c. CONCLUSIONS: SAF is not influenced by short-term glycemic variations. AGE-rich meals may, however, cause a transient rise postprandially. There is a weak correlation between SAF or skin AGEs and current or time-integrated HbA1c levels. SAF has strong added value in risk prediction of complications of diabetes and is a promising tool for early detection of diabetes and IGT.

Advanced glycation end products in renal failure: an overview.

The article aims to present an overview of the existing knowledge on advanced glycation end products (AGE). They are moieties that bind to proteins, but also lipids and nuclear acids. AGE are formed during glycation and oxidative stress. Accumulation of AGE occurs especially in diabetes and chronic renal failure and plays a major pathogenetic role. The deleterious effects of AGE result from cross-linking of proteins and activation of the receptor for advanced glycation end products. AGE accumulation can be noninvasively assessed by the skin autofluorescence reader. In diabetics, the skin autofluorescence predicts cardiac mortality and the occurrence of macro- and microvascular complications. In patients on haemodialysis, skin autofluorescence is highly elevated and predicts mortality. After renal transplantation AGE accumulation is lower than during haemodialysis, but still remains elevated and is a strong risk factor for chronic renal transplant dysfunction. Some of the potential methods to intervene with AGE accumulation are discussed in this article.