Liliana Majkowska

Thoracic spine fracture in the course of severe nocturnal hypoglycemia in young patients with type 1 diabetes mellitus—the role of low bone mineral density☆

Thus far, only a few spine fracture cases related to severe nocturnal hypoglycemia in type 1 diabetes patients have been reported. Due to the relatively young age of these subjects, osteoporosis was not taken into consideration and bone mineral density was not assessed. We report three type 1 diabetes cases in young patients with durations of 2, 4, and 19 years. These patients had severe hypoglycemic attacks during night sleep with subsequent compression thoracic vertebrae fractures. Laboratory parameters for diabetes control, calcium, phosphate metabolism and celiac-specific antibodies were assessed. Moreover, kidney, thyroid, and parathyroid gland functions were also measured. Bone mineral density was assessed by dual energy x-ray absorptiometry. Lumbar spine x-ray absorptiometry revealed very low bone mineral density in all three patients. In all subjects, metabolic control was good, no chronic diabetes complications were found and other laboratory parameters were within a normal range. For the first time, it was demonstrated that low bone mineral density in young type 1 diabetes patients may contribute to an increased compression fracture risk of the dorsal spine during severe nocturnal hypoglycemia courses. The possibility of osteoporosis in young patients with short diabetes durations suggests it might be advisable to perform bone mineral density testing during diabetes diagnoses. Spinal pain occurrences in young patients after severe nocturnal hypoglycemia should be investigated using procedures for the diagnosis of vertebral compression fracture, even if there is no evident trauma.

False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality?

Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a rare autosomal recessive syndrome (1/770,000 in the United Kingdom), characterised by juvenile onset of diabetes mellitus, optic nerve atrophy, diabetes insipidus, sensorineural deafness, renal tract and neurological abnormalities, and primary gonadal atrophy. WS is caused mainly by biallelic mutations in the WFS1 gene, which encodes wolframin. Wide tissue distribution of wolframin and many mutations in the wolframin gene resulting in Wolfram syndrome may contribute to different phenotypes and the unusual combinations of clinical features. We describe a female patient with Wolfram syndrome diagnosed at the age of 25, with a previous false diagnosis of type 1 diabetes mellitus and misdiagnosed diabetic complications. The patient was found to be a compound heterozygote for two novel mutations in exon 8 of WFS1 gene: a 2-bp deletion AT at nt 1539 leading to a frameshift (Y513fs) and a single-base substitution 1174C > T resulting in a stop codon (Q392X). A detailed analysis of the patients medical history and a review of the literature suggest that many cases of Wolfram syndrome may remain undiagnosed due to misdiagnosis as type 1 diabetes mellitus and incorrect interpretation of clinical symptoms of neurodegenerative abnormalities, especially in their early stages.

Clinical and ECG patterns of pseudoinfarction in a young man with type 1 diabetes, diabetic ketoacidosis and normokalaemia

Diabetic ketoacidosis (DKA) can cause changes in the electrocardiogram (ECG) in the form of transient ST-segment depression, QT prolongation, changes in T-wave morphology and the appearance of U wave, possibly due to changes in the serum potassium level. Occasional reports indicate the possibility of transient ST-segment elevation imitating myocardial infarction in the course of hyperkalaemia accompanying DKA. In this article we present a case of a 20-year-old male patient with type 1 diabetes mellitus, DKA and normokalaemia, who experienced severe retrosternal pain, and ECG presented ST-segment elevation imitating acute myocardial infarction of the anterior wall. On the basis of the performed cardiac tests, including laboratory testing, coronary angiography and ultrasound scan, acute coronary syndrome was ruled out. The regression of retrosternal pain and electrocardiographic changes with patient hydration and correction of metabolic disorders suggest the diagnosis of pseudopericarditis, i.e. non-infections irritation of the pericardial membranes due to the loss of fluid in the pericardial sac as a result of dehydration. The diagnosis of acute myocardial infarction based on ST-segment elevation in the ECG recording in a patient with diabetes mellitus and ketoacidosis, without concomitant hyperkalaemia, must be made very carefully, even in the presence of retrosternal pain. The possibility of pseudopericarditis associated with severe dehydration must also be considered.

Existing and potential therapeutic approaches targeting peroxisome proliferator-activated receptors in the management of Type 2 diabetes

The increasing number of patients suffering from Type 2 diabetes generates an urgent need for effective and safe treatment policy. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in cellular metabolism and cell differentiation through the transcriptional regulation of various genes. Their role in lipid and carbohydrate homeostasis has made them an important target for the development of novel therapeutic agents for the management of Type 2 diabetes, dyslipidemia and obesity. Some PPARγ agonists are already in clinical use, but there is a constant search for novel, more potent and safer agents. Development of new technologies, like parallel high-throughput screening, has led to the synthesis and characterisation of dozens of new compounds exhibiting high selectivity towards one or more PPAR subtypes. This review focuses on strategies in developing novel agents targeting PPARs and offering new potential therapeutic benefits in the management of Type 2 diabetes.

Inobvious complications of hypoglycaemia

Tight blood glucose control reduces long-term complications in both type 1 and type 2 diabetes, however increases the risk of hypoglycaemia. The article describes rare acute complications of severe hypoglycaemia — acute pulmonary oedema, stress cardiomyopathy (takotsubo cardiomyopathy) and cardiac arrhythmias including bradycardia or ventricular arrhythmias related probably to QT prolongation. All mentioned acute complications can be life-threatening and lead to sudden death even in young subjects. In some situations they may be misdiagnosed or overlooked.

Czy wzrost częstości zachorowań na cukrzycę typu 1 ma związek z nadmiarem higieny

Liczne badania epidemiologiczne wskazują na staly wzrost czestości zachorowan na cukrzyce typu 1, zwlaszcza w krajach rozwinietych, obserwowany rownolegle ze zmniejszeniem zachorowan na choroby infekcyjne. Wyraźny gradient polnoc–poludnie dotyczący zachorowan na cukrzyce typu 1 i inne schorzenia immunologiczne wystepuje w Stanach Zjednoczonych i Europie, dodatkowo w Europie obecny jest gradient zachod–wschod. W krajach rozwinietych najmniejszą czestośc zachorowan odnotowuje sie na obszarach o najgorszych warunkach socjoekonomicznych i higienicznych. Istnieje kilka hipotez, ktore probują tlumaczyc związek miedzy wiekszą czestością zachorowan na choroby alergiczne i autoimmunologiczne (w tym cukrzyce typu 1) a mniejszą ekspozycją na czynniki infekcyjne. Obejmują one miedzy innymi koncepcje wspolzawodnictwa o antygen, zjawisko „ bystander suppresion ” czy hipoteze „polio”. Zgodnie z hipotezą higieny nadmierne przestrzeganie czystości moze byc przyczyną zaburzonej rownowagi systemu immunologicznego, co z kolei moze prowadzic do procesu autoimmunologicznego skierowanego przeciwko komorkom beta wysp trzustki i bezwzglednego niedoboru insuliny endogennej.