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.

[Primary adrenocortical micronodular dysplasia]. / Primarna adrenokortikalna mikronodularna displazija.

Two girls (11 and 13 years old) with Cushing's syndrome due to primary adrenocortical micronodular dysplasia (PAMD) are presented. High plasma cortisol concentrations, elevated urinary free cortisol and 17-ketogenic steroids excretion, in addition to low or normal plasma adrenocorticotropic hormone (ACTH) levels pointed towards independent adrenal cortisol hypersecretion. In both girls bilateral adrenalectomy was performed, followed by replacement therapy with glucocorticoids and mineralocorticoids. Pathohistological findings of otherwise enlarged adrenal glands, showed characteristic small nodules measuring 1-2 mm, composed of cells resembling those of zona fasciculata, with abundant, clear cytoplasm. Our younger patient fulfilled the criteria of "Carney complex", because beside PAMD she has had the lentigines.

Total plasma antioxidants in first-degree relatives of patients with insulin-dependent diabetes.

Insulin-dependent diabetes mellitus (IDDM) is a chronic disorder that results from autoimmune destruction of the pancreatic beta-cells. Recent evidence suggests that oxidative damage, resulting from both cytokine-induced production of toxic free radicals and low antioxidant capacity of the beta-cell plays a significant role in the pathogenesis of IDDM. Islet cell antibodies (ICA) have been the best validated marker of risk for the development of IDDM in predisposed individuals, i.e. first-degree relatives of patients with IDDM. We investigated the total plasma antioxidant status (TAS) in both ICA-positive and ICA-negative first-degree relatives of patients with IDDM, to assess the level of overall protection against oxidative damage. TAS was significantly lowered in ICA-positive when compared to both ICA-negative and healthy subjects (p < 0.001), while no significant difference was found in comparison to recently diagnosed patients with IDDM. TAS values were not significantly influenced by gender, age and smoking habits in all groups, as well as by ICA titers in the group of ICA-positive subjects. Results indicate that prediabetic condition, apart from well-established immunological and metabolic alterations, could be associated with biochemical changes revealing complex disturbances of the antioxidative defence system. Although TAS is a functional rather than specific marker, its measurement is likely to be a valuable tool for understanding the mechanisms of specific beta-cell injury.

Risk factors for expression and progression of limited joint mobility in insulin-dependent childhood diabetes.

We studied the prevalence of limited joint mobility (LJM) in 100 diabetic children and 100 non-diabetic controls. Our objective was to find possible predictors for the expression and progression of LJM and to evaluate the relationship between LJM and other long-term complications of insulin-dependent diabetes mellitus. LJM was present in 36% of diabetic patients aged 2-20 years. It was significantly related to duration of disease and longitudinal glycated haemoglobin (HbA1c) concentrations, pubertal stage, number of ketoacidosis and skin changes. Fourteen patients had peripheral neuropathy, 16 had microalbuminuria, 8 had nephropathy, and 7 had retinopathy. After matching for duration of disease, HbA1c concentrations and pubertal stage, a comparison of the complication rates was made. All long-term complications were significantly associated with LJM. Longer duration of disease and higher mean longitudinal glycated haemoglobin level are independent predictors for expression of LJM. Thus, improvement of metabolic control in diabetic patients before puberty may diminish the expression and progression of LJM.

Incidence of IDDM during 1988-1992 in Zagreb, Croatia.

The objective of this study was to determine the incidence of insulin-dependent diabetes mellitus (IDDM) in the population of Zagreb, Croatia, during 1988-1992. A centralized diabetes registry was the primary source of data, while secondary sources were used to assess ascertainment. A total of 282 new cases of IDDM were diagnosed in the study period, the primary and secondary sources identifying annually 93-100% of the cases. The annual incidence rate ranged from 5.6 per 100,000 to 6.6 per 100,000. Early fatality in persons older than 50 years was the major cause of underascertainment. The incidence peaked in the 10-14 years age group (12.4 per 100,000), and remained stable after age 24 years. Males had a significantly higher incidence in the 5-9 and 24-44 years age groups. In the 45-54 years age group, females had a significantly higher incidence. No seasonality was observed. Despite the war conditions in Croatia, the low overall IDDM incidence rates did not change significantly during the study period.

Apolipoprotein E phenotypes and genotypes as determined by polymerase chain reaction using allele-specific oligonucleotide probes and the amplification refractory mutation system in children with insulin-dependent diabetes mellitus.

The frequency of apolipoprotein E (apo E) phenotypes and genotypes due to allelic variation at amino acids 112 and 158 was analysed in 50 children with type I diabetes. Phenotypes were determined by isoelectric focusing and genotypes by the technique of polymerase chain reaction using allele-specific oligonucleotide probes (PCR/ASO) and the amplification refractory mutation system (ARMS). Discrepancies between phenotypes and genotypes as assigned by PCR/ASO were observed in 12 (24%) cases and by ARMS in eight (16%) cases. Results revealed the apo E3/3 genotype, as assigned by ARMS, to be the most frequent one (70%), followed by apo E3/4 in 16%, apo E2/2 in 2%, apo E2/3 in 8%, apo E2/4 in 2% and apo E4/4 in 2% of the cases. Apo E3/4 genotype and phenotype were more frequently present in the children with type I diabetes as compared with the diabetic adults previously reported on.

Polymorphism of apolipoprotein E, lipoprotein(a), and other lipoproteins in children with type I diabetes.

We assessed the effect of particular apolipoprotein (apo) E phenotypes, lipoprotein(a) [Lp(a)], and other lipoproteins on the development of dyslipoproteinemia in 450 patients with type I diabetes, ages 13-14 years. The control group consisted of 450 healthy school children of both sexes, ages 13-14 years. Both groups were found to be normolipidemic, but the concentration of Lp(a) was significantly (P < 0.05) higher in the diabetic children than in the control group. Apo E 3/2 and apo E 4/4 phenotypes were more frequent in the group of diabetics. Diabetics with the apo E 3/3 phenotype had higher concentrations of very-low-density lipoprotein (VLDL) and Lp(a), and lower concentrations of low-density lipoprotein (LDL) than the apo E 3/3 nondiabetics. For apo E 3/2 phenotypes, total cholesterol, LDL cholesterol, LDL, apo A-I, and Lp(a) concentrations were higher in the diabetic children than in the control group; for apo E 4/3 phenotypes, this was true for triglycerides and VLDL cholesterol. The distribution of Lp(a) lipoprotein concentrations between 0.01 and > 0.5 g/L indicated a more frequent occurrence of higher Lp(a) values in diabetic children than in the control group. Results of this study indicate that an increased concentration of Lp(a) lipoprotein and apo E 3/2 and apo E 4/3 phenotypes contribute to the expression of dyslipoproteinemia in type I diabetes in childhood.

[The femoral hypoplasia syndrome and unusual facies in an infant of a diabetic mother]. / Sindrom hipoplasticnih femura i neobicnog lica u djeteta majke dijabeticarke.

One-month-old female infant of diabetic mother with the femoral hypoplasia--unusual facies syndrome is presented. At birth the characteristic facial pattern of long philtrum with thin upper lip, micrognathia and cleft palate was present. Both legs showed extreme shortening of the upper segments. X-rays showed numerous skeletal abberations including radioulnar synostosis of the right elbow, dysplastic sacrum and hypoplasia of the femurs, the right one more severe. Radiological findings also revealed abnormal left kidney's collecting system and absence of the right kidney. Possible contributing factors to the pathogenetic mechanism underlying the skeletal defects in infants of diabetic mothers are considered.

Adrenocorticotropic hormone insensitivity associated with autonomic nervous system disorders.

Five children with adrenocorticotropic hormone (ACTH) insensitivity associated with autonomic nervous system disorders are described. At the time of diagnosis, four of them had osteoporosis. The fifth patient died and skeletal roentgenograms were not done. Osteoporosis was subsequently discovered in one of our previously reported patients with ACTH insensitivity. We assume that osteoporosis is, at least partly, the result of decreased adrenal androgen production. Human leucocyte antigen typing failed to establish any linkage.

An update on the frequency of nonclassic deficiency of adrenal 21-hydroxylase in the Yugoslav population.

Nonclassic steroid 21-hydroxylase deficiency is an attentuated adrenal enzyme defect that is commonly the basis of hyperandrogenic syndromes. Inherited as an autosomal recessive trait, it is known to occur with high frequency in the general population and with increased frequency in a number of ethnic groups, including the Yugoslav population. Following expansion of the original data on 21 families in Croatia to a total of 49 Croatian and Serbian families, we establish that this enzymatic disorder is increased in this Slavic population and provide an updated estimate for the gene frequency of 0.092 (0.035-0.149). Also in keeping with earlier reports, we continue to note the absence of association between nonclassic 21-hydroxylase deficiency occurring among Yugoslavs and HLA-B14; DR1.

Selective ACTH insensitivity associated with autonomic nervous system disorders and sensory polyneuropathy.

A 10-year-old boy is described with a syndrome of adrenal insufficiency due to selective ACTH insensitivity associated with autonomic nervous system disorders. In addition to insufficient production of glucocorticoids and adrenal androgens, achalasia, defective lacrimation, anisocoria and hyperkeratosis of palms and soles we also found defective sweating, permanent cutis anserina and sensory polyneuropathy, which have not been reported previously in this rare syndrome.