Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes.

AIMS: Metformin is the most widely used oral anti-diabetes agent and has considerable benefits over other therapies, yet 20-30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter-individual variability is unclear. We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes. METHODS: This prospective observational cohort study included 92 patients with newly diagnosed Type 2 diabetes, incident users of metformin. Patients were genotyped for two common loss-of-function variants in the OCT1 gene (SLC22A1): R61C (rs12208357) and M420del (rs72552763). The association of OCT1 reduced-function alleles with gastrointestinal side effects was analysed using logistic regression. RESULTS: Forty-three patients (47%) experienced gastrointestinal adverse effects in the first 6 months of metformin treatment. Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034). CONCLUSIONS: In conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects. These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. These data could contribute to more personalized and safer metformin treatment.

Neonatal alloimmune thrombocytopenia caused by anti-HLA-A24 alloantibodies.

UNLABELLED: Neonatal alloimmune thrombocytopenia (NAIT) occurs as a result of maternal alloimmunization against paternally inherited antigens on foetal platelets. Platelets express platelet specific antigens (HPA) along with human leucocyte antigens (HLA) class I. Although anti-HLA class I antibodies are often detectable in pregnant women, their role in NAIT is considered controversial. We report a case of NAIT where the most sensitive serological analysis and molecular methods could not detect platelet specific antibodies. Only HLA incompatibility and presence of anti-HLA-A24 antibodies in both the mother's and the newborn's serum were proven. CONCLUSION: This case supports the idea that some anti-HLA class I antibodies could cause NAIT.

Incidence and trends of childhood Type 1 diabetes in Croatia from 1995 to 2003.

AIMS/HYPOTHESIS: The aim of this study was to examine incidence and trends of Type 1 diabetes in children aged 0-14 years in Croatia from 1995 to 2003. METHODS: The incidence data were obtained from two sources. The incidence was calculated as the number of newly diagnosed Type 1 diabetes patients per 100,000 person-years for the age group 0-14 years, and subgroups 0-4, 5-9, and 10-14 years. Standardized incidence was calculated using the method of direct standardization to the world standard population for the age group 0-14 years. The ascertainment was estimated with capture-recapture method. Trends in the incidence of Type 1 diabetes for period from 1995 to 2003 in Croatia were analyzed using Poisson regression model. RESULTS: The standardized incidence of Type 1 diabetes for the whole age group was 8.87 per 100,000 person-years (95% CI: 5.07-12.68), for girls 8.47 (95% CI: 7.54-9.41) and for boys 9.26 (95% CI: 8.30-10.21). During the studied period, the trend in incidence raised significantly for the whole age group (chi(2)=32.6, p<0.001). The average annual increase in incidence was 9% (95% CI: 5.8-12.2). CONCLUSIONS/INTERPRETATION: This rate of incidence places Croatia in a group of countries with moderate risk for development of Type 1 diabetes. The average annual increase in incidence of 9% is markedly higher than in most European countries, and probably reflects lifestyle changes upon economic recovery of the country.

Epidemiological, forensic, clinical, and imaging characteristics of head injuries acquired in the suicide attempt with captive bolt gun.

The captive bolt gun (slaughterer's gun) is a tool used in the meat industry for "humane killing" of animals. Used with the intent of suicide, the captive bolt gun causes very serious injuries. We analysed 19 self-inflicted head injuries with captive bolt gun during the past 20 years. Autopsy of 20 pigs killed by this method was also performed. All 19 cases were middle-aged men from rural areas, with low level of education, and without a previous psychiatric history. Five of them used the captive bolt gun daily in their professional activities, while the remaining 14 handled it only sometimes. In seven cases suicide was primarily successful, while in five patients, despite intensive medical care, serious craniocerebral injuries eventually resulted in death. Total mortality was 63.2%. The clinical appearance of the entrance wound and the imaging characteristics of the cranial trauma are very specific, and can be easily differentiated from firearm or other penetrating injuries. These wounds were always primarily infected with mixed bacterial flora from the skin. Therefore, besides radical primary wound care, especially of the wound canal with removal of foreign bodies, it is important to administer high doses of wide spectrum antibiotics.

Chiasma syndrome in acromegalic patients--correlation of neuroradiologic and neuroophthalmologic findings.

The study evaluated neuroophthalmologic and computerized tomography (CT) findings in 100 patients with somatotrophic adenoma and clinical picture of acromegaly, who underwent transsphenoidal adenomectomy. Prior to the surgery, visual field was normal in 77 patients. The diameter of adenoma in these patients ranged from 8 to 30 mm on CT, and the average value was 13.5 mm. Various kinds of visual field disturbances were present in 23 patients. The diameter of their adenomas ranged between 18 to 35 mm, with the average of 24.7 mm. Compared to visual field defects, CT findings of suprasellar adenoma extension were better correlated with chiasma syndrome (p < 0.001). All patients with suprasellar mass greater than 10 mm had chiasma syndrome. Degenerative adenoma changes (hemorrhagic necrosis), which precipitate abrupt increase in size of the tumor, were more frequently seen in patients with chiasma syndrome. The incidence of chiasma syndrome directly correlates with the degree of suprasellar extension of the tumor.