Persons with latent autoimmune diabetes in adults express higher dipeptidyl peptidase-4 activity compared to persons with type 2 and type 1 diabetes.

AIMS: We aimed to determine serum dipeptidyl peptidase-4 (DPP-4) activity in a group of persons with latent autoimmune diabetes in adults (LADA) and to compare it with persons with type 1, type 2 diabetes and healthy controls. METHODS: DPP-4 activity measurement was performed in 67 persons (21 with type 1, 26 type 2 and 19 with LADA) and 13 healthy age and gender matched controls. RESULTS: Persons with LADA showed highest DPP-4 activity among the study groups (32.71±3.55 vs 25.37±2.84 vs 18.57±2.54 vs 18.57±2.61U/L p<0.001). Mean glutamic acid autoantibody in persons with LADA was 164.32±86.28IU/mL. It correlated with DPP-4 activity (r=0.484, p=0.013). Furthermore, DPP-4 activity correlated with waist circumference (r=0.279, p=0.034) and glycated haemoglobin A1c (r=0.483, p<0.001), as well as with LDL cholesterol (r=0.854, p<0.001) and total daily insulin dose (r=0.397, p=0.001). In the multinomial regression analysis DPP-4 activity remained associated with both LADA (prevalence ratio 1.058 (1.012-1.287), p=0.001) and type 1 diabetes (prevalence ratio 1.506 (1.335-1.765), p<0.001) while it did not show an association with type 2 diabetes (prevalence ratio 0.942 (0.713-1.988), p=0.564). CONCLUSIONS: Persons with LADA express higher DPP-4 activity compared to persons with both type 1 and type 2 diabetes. The possible pathophysiological role of DPP-4 in the LADA pathogenesis needs to be further evaluated.

Comparison of antihyperglycemic effects of creatine and metformin in type II diabetic patients.

PURPOSE: To compare the antihyperglycemic effects of metformin and creatine in recently detected type II diabetics in a short-term clinical study. METHODS: In a 14 day simmetrically randomized crossover study, recently detected type II diabetics received either creatine (2x3 g/day) or metformin (2x500 mg/day) for five days, followed by two days of washout, followed by cross-over to the opposite treatment for the next five days. Fasting and post-prandial (-15, 60, 90, 120, 180 and 240 min) blood glucose, insulin, c-peptide, creatine and lactate were measured every other day for the duration of treatment, and HbA1c only at the begining and at the end of the study. RESULTS: Both creatine and metformin decreased glucose concentrations to similar levels at all time points vs. basal glucose values [-15, 60, 90, 120, 180, and 240 min]: 11.1+/-0.75 vs 9.1+/-0.55a vs 8.8+/-0.59b, 14.4+/-0.6 vs 12.9+/-0.47a vs 13.1+/-0.55a, 14.8+/-0.58 vs 13.0+/-0.46b vs 13.3+/-0.55a, 14.1+/-0.6 vs 11.9+/-0.42b vs 12.5+/-0.51a, 12.2+/-0.6 vs 9.6+/-0.36c vs 9.9+/-0.38c, and 10.1+/-0.47 vs 7.8+/-0.36c vs 8.4+/-0.4b; (aP < 0.05; bP < 0.01; cP < 0.001 vs. basal glucose values). Neither treatment altered insulin, c-peptide, or HbA1c. Lactate varied during the day, but never reached the upper level of the safety reference range. CONCLUSION: Short-term treatment with creatine and metformin elicits similar glucose lowering effects in recently detected type II diabetics. Further studies are necessary to determine the effect of creatine on long-term glucose and insulin regulation.

Effect of creatine on the pancreatic beta-cell.

We report on the stimulatory effect of creatine on insulin secretion and ATP concentration in MIN-6 beta-cells. The addition of creatine (5 mM) to MIN-6 cells in the presence of glucose (1-10 mM) elicited a significant (p<0.001) increase in insulin secretion, but no effect was demonstrated in the absence of glucose. The lack of effect of creatine in the absence of glucose suggests that creatine may act as a potentiator of insulin secretion rather than as an initiator. The potentiatory effect of creatine is specific for glucose since no effect was found in the presence of other known initiators of insulin secretion (K(+), 2-ketoisocaproic acid and tolbutamide). Cellular ATP content was markedly increased by glucose (1-15 mM). Creatine (5 and 10 mM) further increased the ATP level at all glucose concentrations, and the effect was observed even in the absence of glucose. The results from this study demonstrate the ability of creatine to increase insulin secretion only in the presence of glucose, while its effect on increased cellular ATP was independent of the presence of glucose. The mechanism whereby creatine potentiates insulin release is yet to be investigated. However, our data suggest possible unique interactions between creatine and the glucose-dependent insulin secretory pathway.

Screening of patients with Turner syndrome for "hidden" Y-mosaicism.

The presence of Y-chromosomal sequences in the cells of patients with Turner-Syndrome (TS) is a risk factor for the development of gonadal tumors. Therefore and since demonstration of Y-material usually results in prophylactic gonadectomy optimal sensitivity and specificity of the diagnosis have to be attempted. We wanted to evaluate the diagnostic potential of cytogenetic investigations as routinely employed in TS. In the most comprehensive study published so far we screened 208 TS patients for the presence of Y-chromosomal sequences by polymerase chain reaction (PCR) specific for eight different loci along the Y-chromosome. Six patients (3%) without cytogenetic evidence of Y-chromosome were found to be Y-positive. Among 12 cases with marker chromosomes two more Y-chromosomal fragments were identified. Thus, PCR-screening for Y-specific sequences was shown to be a valuable tool in the clinical management of Turner patients.

Frequency of Hashimoto's thyroiditis in children with type 1 diabetes mellitus.

A total of 1419 children with type 1 diabetes mellitus was investigated in order to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT were identified, a number significantly higher (P < 0.0001) than the distribution reported in the normal paediatric population. No typical antibody pattern was seen prior to the onset of HT, nor was an antibody threshold level found which could have been diagnostic for this disease. Patients with subclinical hypothyroidism were treated with L-thyroxine and were investigated regarding the behaviour of anti-thyroid autoantibodies; however, no significant changes were seen. The data showed a high frequency of HT in diabetic children, and therefore we recommend that children with type 1 diabetes mellitus should be screened for thyroid autoantibodies and those positive should undergo periodic thyroid function testing.

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.

Diagnostic value of growth hormone-releasing hormone tests in short children.

The values of GH following GHRH stimulation were determined in 32 short children. Firstly, the secretion of GH was measured by two conventional tests (insulin-induced hypoglycemia and arginine tests). According to the response of GH secretion, the children were divided in two groups, the first one with short children suffering from growth hormone deficiency (GHD) (N = 17), and the second with short children without growth hormone deficiency (non-GHD) (N = 15). In the first group (GHD), according to the extent of the GH response to GHRH stimulation, three subgroups were distinguished: in 8 children GH response was < 5 ng/ml, in 5, between 5 and 8 ng/ml, and in 4 the response was > 10 ng/ml. In the second group (non-GHD), the response of GH was between 4.7 and 8.2 ng/ml only in two children, and all other children expressed a response above 10 ng/ml. Comparing the values in both groups by induced hypoglycemia and GHRH test, the response of GH was significantly higher following GHRH stimulation. In the first group the mean value of GH following GHRH stimulation was 10.9 ng/ml (s = 16.35), and in induced hypoglycemic test 1.92 ng/ml (s = 1.86). In the non-GHD group the mean value of GH in the GHRH test was 25.29 ng/ml (s = 14.15), versus GH value in the hypoglycemic test of 11.22 ng/ml (s = 3.045). The authors conclude that the GHRH stimulation test is an acceptable test in differentiation between GH deficiency of pituitary and hypothalamic origin. Still, the GHRH stimulation test alone is not sufficient for the diagnostic procedure of GH deficiency.

Transcranial Doppler diagnostic criteria in the evaluations of arteriovenous malformations.

In order to get a better insight in hemodynamic occurrence of intracranial arteriovenous malformations (AVM), 31 patients with AVM, documented by CT and angiography, were investigated by Transcranial Doppler (TDC). Although the angiography provides definite diagnosis of AVM, its size, position, type feeders and involvement of various vascular segments, TCD provides more information about collateral circulation, intracerebral shunts or functional stenosis due to high blood velocities within the blood vessels involved by AVM. The parameters obtained by TCD: mean cerebral blood flow velocities (MCBFV) in middle and internal carotid artery (MCA, ICA), pulsatility index (PI), MCA/ICA ratio and (S-D)/S ratio were introduced. Results have shown that TCD findings in non-feeding arteries were normal in all patients. TCD finding of MCBFV in MCA and ICA, PI and MCA/ICA ratio in feeding arteries has shown a significant difference from normal arteries (p less than 0.01). These parameters are shown to be AVM size dependent. MCBFV in MCA on the feeder side was statistically significant higher in those patients with large AVM (greater than 4 cm) size (p less than 0.01). For assessment of AVM and its improved and advanced analysis the potential advantages of parameters: (S-D)/S ratio and 3D hemodynamic mapping has been emphasised.

Duplex scanner versus conventional arteriography for carotid artery disease evaluation.

In order to evaluate extracranial circulation, Duplex scanning and conventional angiography were performed. The group of 41 patients (mean age 53.8 +/- 11.8, 71% male) were examined. Results were analyzed for extracranial disease presence such as presence of vessel stenosis (mild, moderate, severe), occlusion and presence of plaques. Data from Duplex scanning and carotid arteriography were correlated within the patients in the term of sensitivity and specificity of the methods used. The sensitivity of Duplex scanning for disease presence was 93% and specificity was 83%. For the presence of stenosis, sensitivity was 79% and specificity was 62%. For mild and moderate stenosis (less than 50% of lumen narrowing) sensitivity was 63%, whereas for severe, high-grade stenosis (greater than 50%) and occlusion the sensitivity was 100%. For the plaque presence the sensitivity was 52% and specificity was 73%. A good accordance of plaque findings with both methods was found only in 24% of patients. By Duplex scanner the plaques were discovered in 92% of patients while by arteriography they were found only in 32%. Duplex scanning and conventional arteriography are both accurate methods for determination of the reduction in diameter of carotid arteries (especially in stenosis greater than 50%), whereas Duplex scanning is more accurate for plaque detection and plaque characterisation.

Daily iodine intake in healthy children and adults and in goitrous patients in nonendemic Yugoslav area.

Daily iodine intake has been investigated in 52 healthy children (5-14 years), 112 healthy adults and in 39 patients with nontoxic goiter from the area of Zagreb/Yugoslavia. Fourteen goitrous patients received 1-thyroxine 150 micrograms daily for at least three months before the examination. Iodine intake has been estimated on the basis of urinary iodine excretion (microgram I-/g creatinine) in the first morning specimen. Iodine excretion in nontreated goitrous patients (92 +/- 30; Mean +/- SD) was significantly lower than in healthy adults (112 +/- 38), while the value in treated goitrous patients (165 +/- 69) was significantly higher than that in nontreated goitrous and healthy adult subjects. The results suggest that Zagreb area, although classified as nonendemic, has borderline iodine intake, and that relative iodine deficiency is of importance in goiter formation. The authors plead for increased daily iodine intake through increased table salt iodisation from actual amount of 10 to 20 to 25 mg KI/kg salt in order to provide an average daily intake of 250 micrograms of iodine.

Iohexol versus meglumine-Ca-metrizoate in cerebral angiography. A randomized double-blind cross-over study.

The tolerance and suitability of iohexol in cerebral angiography was compared in a clinical trial with meglumine-Ca-metrizoate in 20 patients. A preference for iohexol after injection into the external carotid artery in a paired comparison was established in 84.2 per cent of the patients. The difference was also statistically significant (p less than 0.01) with regard to the intensity of discomfort estimated according to a four grade scale. The milder sensations occurred more frequently with iohexol (1.21), while moderate as well as severe reactions were caused by metrizoate (2.78). These reactions caused discomfort and occasionally movements, with blurring of the films. Both contrast media provided sufficient information to enable an accurate radiologic diagnosis.