COMPLIA: A 12-MONTH PROSPECTIVE, MULTICENTRE, NON-INTERVENTIONAL STUDY TO EVALUATE TREATMENT ADHERENCE AND TREATMENT SATISFACTION IN A GROWTH HORMONE DEFICIENT PAEDIATRIC POPULATION TREATED WITH NUTROPINAQ® A SOMATROPIN ANALOGUE.

BACKGROUND/AIMS: Growth hormone deficiency (GHD) in children and adolescents is managed with growth hormone (GH) therapy and aims to achieve optimal height development. However, treatment adherence can be poor, reducing the likelihood of a successful outcome. Adherence varies between geographic regions. This observational study assessed satisfaction and adherence to NutropinAq (somatropin, recombinant human GH) treatment in Romanian children with GHD. METHODS: Patients ≥3 years of age with GHD for which GH replacement therapy with NutropinAq had been initiated were recruited from 13 centres in Romania (protocol number: A-38-58035-016). The primary variable was patient/caregiver-reported treatment adherence (assessed at 3, 6 and 12 months on a 5-item Likert scale), secondary variables included treatment satisfaction assessed by the treating physician and patient/caregiver on a 5-point scale. RESULTS: Most patients did not miss any treatment injections in any 3-month period between assessments (≥79.8% of patients were 100% compliant). The incidence of missed injections was higher among patients <7 years of age than older children, but no differences between genders was observed. At study end, 94.3% of patients/caregivers and 94.3% of physicians reported complete satisfaction with treatment. CONCLUSIONS: Overall treatment adherence to NutropinAq was high in the Romanian GHD paediatric population, and a high level of treatment satisfaction was reported by patients/caregivers. This suggests reliable treatment outcomes can be anticipated in this population.

Epidemiological and Histopathological Aspects of Tongue Squamous Cell Carcinomas-Retrospective Study.

Tongue squamous cell carcinoma is one of the most commonly diagnosed intraoral squamous cell carcinomas (25-40%), being considered an aggressive form of squamous cell carcinoma, as it is most commonly associated with lymph node metastases and the survival rate at five years is below 50%. In according with these data, we have proposed in this study to individualize an epidemiological and histopathological profile of the patients with such oral cancers, diagnosed and treated in the Oral and Maxillofacial Surgery Clinic and in the Otolaryngology Surgery Clinic of the Emergency Clinical County Hospital Craiova, between 2015-2017. The cases were histopathologically reassessed according to the latest WHO classification of head and neck tumors, the variables of interest being the age of the patients, the gender, the lesion topography, the histological subtype, the degree of tumor differentiation, the pTNM stage, the resection margin status and the Brandwein-Gensler prognostic score. Thus, we recorded an average age of 55.81±14.98 tongue cancer development, 65% of the casuistry being diagnosed during the 7th and 6th decades, with a slight prevalence in men, with development in two thirds of cases in the mobile portion of the tongue. Histopathologically, conventional forms of squamous cell carcinoma prevailed (53.7%), followed by varieties: acantholytic (26%), basaloid (13%), sarcomatoid (5.45%) and verrucous (1.85%). Moderate differentiated forms prevailed (44.44%), half of the cases falling within the moderate degree of Brandwein-Gensler's histological risk score and two thirds were diagnosed in pTNM stage II and III of the disease, and a quarter of the cases having the margins invaded.

Sleep and Memory Disorders in a Patient Suffering from Charcot-Marie-Tooth Disease.

Currently incurable, Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder, which affects a small percentage of the population. The most common cause of CMT is the duplication of a region on the short arm of chromosome 17, which includes the gene PMP22. We report a thirty-seven-year-old man with CMT disease having sleep, memory and attention disorders characterized by brief retrograde amnesia at early age. The patient has no genetic disease in the family, but was diagnosed with diabetes mellitus, which emphasizes the sensory loss and prolonged infections. Diabetes mellitus emphasizes the sensory symptomatology and predisposes to the development of infections with delayed healing.

Stability and degradation of fibroblast growth factor 23 (FGF23): the effect of time and temperature and assay type.

UNLABELLED: There is growing need for a reliable assay for measuring fibroblast growth factor 23 (FGF23), a regulator of phosphorus and vitamin D. In this work, we analyze and compare the performance of three available assays, including the effect of temperature and time. This knowledge will allow for better understanding of FGF23 in the future. INTRODUCTION: Intact and C-terminal FGF23 (iFGF23 and cFGF23) concentrations are important in the diagnosis of hypo- and hyperphosphatemic diseases. The effects of temperature, storage, and specimen handling on FGF23 levels are not well known. We investigated the effects of various factors on plasma and serum measurement of FGF23 using three different assays. METHODS: Serum and plasma FGF23 were measured using three commercially available ELISA assays-two measuring iFGF23 and one measuring cFGF23. Samples from subjects with known FGF23 disorders were stored at 4, 22, and 37 °C and analyzed at different intervals up to 48 hours (h). A subset of samples underwent repeated freeze-thaw cycles, and samples frozen at -80 °C for up to 60 months were reanalyzed. The effect of adding a furin convertase inhibitor on FGF23 degradation was investigated using samples stored at 37 °C for 48 h. Intact FGF23 levels were measured from plasma samples of four different groups to test the correlation of the two assays. RESULTS: Plasma FGF23 levels were stable when stored at 4 and 22 °C for 48 h. Both plasma and serum FGF23 levels demonstrated relative stability after five freeze-thaw cycles. Long-term storage at -80 °C for 40 months induced some variability in FGF23 levels. The addition of a furin inhibitor did not affect FGF23 degradation. Intact FGF23 levels showed good correlation only at the upper limit of the assay range when comparing the two assays. CONCLUSIONS: Sample type, handling, and choice of assay are factors that affect FGF23 levels and should be considered when measuring this hormone.

DEVELOPMENT OF SYNTHETIC GROWTH CHARTS FOR ROMANIAN POPULATION.

There are no new national growth references for the Romanian population and the current recommendations for short stature evaluation is the use of the Swiss growth charts developed based on a longitudinal study.The aim of the present paper is to present the new synthetic growth references for Romanian children. MATERIAL AND METHODS: We used local Romanian data from 9 studies with information on height and weight obtained between 1999 and 2016. Based on their plausibility and methodology six studies were selected for generating the National Synthetic Growth References for Romanian Children based on the specific methodology described previously. The selected studies included 8407 subjects measured in schools/kindergartens. Age is reported in years covering a range from 3-18 years. Height and weight were measured at a precision of 0.1 cm and 0.1 kg. All children were measured at normal temperature, in light clothes, without footwear. RESULTS: We present the charts and tables with the common centiles for height, weight and body mass index for boys and girls. CONCLUSION: We suggest synthetic growth references based upon recent growth data from 6 different Romanian regions as new National Growth Charts for Romanian children.

Phenotypic spectrum and hormonal profile in hypogonadotropic hypogonadism.

BACKGROUND: Hypogonadotropic hypogonadism (HH) is characterized by inappropriately low serum concentration of LH (luteinizing hormone) and FSH (follicle-stimulated hormone) in the setting of hypogonadism. A number of pathologic processes cause Hypogonadotropic hypogonadism but it can also occur as a part of various congenital syndromes. Objectives. To characterize the morphotypes and the hormonal profile of the HH patients enrolled in the COST Action BM1105 within "C.I. Parhon" National Institute of Endocrinology from May 2012 onward. Methods. The eligible patients were selected by using a general protocol that included: a detailed familial and personal history; a clinical evaluation focusing on genital development; a hormonal evaluation that aimed to exclude the acquired causes of HH and to characterize the basal/stimulated (triptoreline) profile of gonadotropins; a DNA extraction for genetic studies. RESULTS: We examinated the medical records of patients admitted in our institute with the diagnosis of hypogonadotropic hypogonadism from May 2012 onward. There were 19 patients: 12 males and 7 females, age at diagnosis 28.03 ± 11.45 years (13.4-56 years). The phenotypic expressions were variable and the hormonal evaluation showed low values of basal and stimulated gonadotropins. CONCLUSIONS: Although hypogonadotropic hypogonadism is a rare disease, the monospeciality profile of National Institute of Endocrinology enable the enrolment of a high number of patients in order to create clinical guidelines for evaluation/diagnosis and for treating GnRH deficient patients.

A case of familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome due to a compound heterozygous mutation in GALNT3 demonstrating new phenotypic features.

SUMMARY: A new case of familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) due to a novel compound heterozygous mutation in N-acetylgalactosaminyltransferase 3 (GALNT3) and with new phenotypic findings is presented. The response in serum phosphate and fibroblast growth factor 23 (FGF23) to medical treatment is detailed. This case expands the genotype and phenotype of FTC/HHS and gives insight into its treatment and pathophysiology. INTRODUCTION: FTC and HHS are caused by mutations in FGF23, GALNT3, or KLOTHO. They are characterized by hyperphosphatemia, increased phosphate reabsorption, and elevated or inappropriately normal serum 1,25-dihydroxyvitamin D(3) (1,25-D(3)); FTC is associated with calcific masses, and HHS with diaphyseal hyperostosis. METHODS: A 36-year-old woman presented with abnormal dental X-rays at age 12 and was hyperphosphatemic at 22. She underwent radiographic, biochemical and genetic testing, and medical treatment. RESULTS: Serum phosphorus was 7.3 mg/dL (2.5-4.8), TmP/GFR 6.99 mg/100 mL (2.97-4.45), 1,25-D(3) 35 pg/mL (22-67). Radiographs revealed tooth anomalies, thyroid cartilage calcification, calcific masses in vertebral spaces, calcification of the interstitial septa of the soft tissue in the lower extremities, and cortical thickening of the long bones. Her total hip Z score was 1.9. C-terminus serum FGF23 was 1,210 RU/mL (20-108), but intact FGF23 was 7.4 pg/mL (10-50). DNA sequencing determined she was a compound heterozygote for mutations in GALNT3. Treatment with niacinamide and acetazolamide decreased TmP/GFR and serum phosphate, which was paralleled by a decrease in serum C-terminus FGF23. CONCLUSIONS: This case broadens the spectrum of phenotypic and genotypic features of FTC/HHS and suggests treatments to decrease renal phosphate reabsorption in the setting of a low intact FGF23.

[Evaluation of ventricular asynchronism by Doppler tissue imaging in patients with idiopathic dilated cardiomyopathy]. / Evaluation de l'asynchronisme ventriculaire par échocardiographie Doppler tissulaire chez les patients atteints d'une cardiomyopathie dilatée idiopathique à QRS fins.

OBJECTIVES: To study ventricular asynchronism with tissue Doppler imaging in patients with primitive dilated cardiomyopathy and narrow QRS. PATIENTS AND METHODS: We compared a group of patients with DCM and QRS < 120 ms (gr 1, n=25, 52+/-14 yrs, LVEF: 25+/-9%) with a group of normal patients (gr 2, n=16, 36+/-20 yrs). We measured the delays between the beginning of QRS and the beginnings of aortic (QA), mitral (QM), tricuspid (QT) and pulmonary (QP) flows, and of systolic (QSm) and protodiastolic (QEm) wall motion waves recorded with TDI in the basal portion of interventricular septum (IVS) and LV and RV free walls. We then calculated the differences QA-QP, QM-QT, the interparietal differences for QSm and QEm, and the maximal interparietal systolic (QSm max) and diastolic (QEm max) delays. RESULTS: QA, QP, QM and QT were significantly lengthened in group 1 patients but there were no difference between both groups for QA-QP and QM-QT. There was a trend toward a lengthening of QSm and QEm in group 1 patients. Interparietal differences of QSm and QEm were similar in both groups; however, QSm max and QEm max were significantly longer in group 1 patients than in group 2. CONCLUSION: Doppler study of patients with DCM and narrow QRS shows a lengthening of all electromechanical delays and suggests some degree of ventricular asynchronism by showing a significant increase in maximal interparietal systolic and diastolic delays.

[Hereditary pancreatitis]. / Pancreatita ereditara.

We present the cases of three brothers (a woman and two men) with recurrent attacks of necrotic acute pancreatitis that were treated in our clinic. Two of them have diabetes mellitus controlled through insulin treatment. All patients have presented the first episode of acute pancreatitis around age of 35. We have observed a high level of serum triglyceride at admission, without evidence of lipid disorder. In addition we couldn't identify other causes of these episodes of acute pancreatitis (biliary stones, alcohol, trauma, drugs, lipid disorders). During the last year two members of this family presented recurrent attacks of abdominal pain without any biochemical or imaging signs of acute pancreatitis.

[Gastric stromal tumors--Clinical and histopathological analysis of four cases]. / Tumori gastrice stromale--analiza clinica si histopatologica a patru cazuri.

BACKGROUND: The aim of this study is to present our experience concerning a rare form of gastric tumor--gastrointestinal stromal tumor (GIST). METHODOLOGY: We reviewed data of four patients with gastric stromal tumors, which have been admitted in our department from 1998-2002. RESULTS: There were two females and two males with age of 75, 70, 65 and 63 years old. The average duration of symptoms until hospital admission was 7 days. During surgery we discovered proximal gastric tumors with 4, 5, 10 and 20 cm in largest diameter. We performed excision of the whole tumor with a security limit of 2 cm or gastric resection (one case), without limphadenectomy. One patient developed an anastomotic fistula with a good evolution under conservative treatment. All patients left the hospital in a good condition. Histopathological and immunohistochemical study diagnosed gastric stromal tumors by identifying the CD 117 maker. Postoperatively neither one of our patients received chemotherapy or radiotherapy. One female and one male patient died of peritoneal metastasis at nine months and respectively two years after operation. The other two patients are in a good condition up to date, without metastasis, one and respectively three years after surgical treatment. CONCLUSIOUS: Correct diagnosis, complete tumor resection and surveillance are essential steps in management of gastric stromal tumors.

Results obtained in the metrological certification of a commercially available radionuclide calibrator.

The paper presents the results obtained at IFIN-HH during a metrological certification of the commercially available radionuclide calibrator, the CURIEMENTOR2. Its performance was tested for the radionuclides: 57Co, 99mTc, 131I and 137Cs. The calibration factors determined by the manufacturer and those obtained at IFIN-HH differed by less than 3.5%. New calibration factors were determined for 60Co and 188Re, which have, until now, not been distributed by the manufacturer to the users. Furthermore, the linearity of instrument response and the dependence of measuring geometry were checked and found in accordance with the international accepted standards and legal requirements.

Clinical manifestations in the West Nile virus outbreak.

During the summer of 1996 an unusual clustering of meningoencephalitis cases was recorded in the Capital City, Bucharest, and in some areas from South-East Romania. After an initial suspicion of an enteroviral etiology was discarded, the West Nile etiology was confirmed by specific antibodies demonstration through hemagglutination-inhibition and ELISA tests. This study included 251 patients with the diagnoses of West Nile acute encephalitis (166 cases), acute meningitis (57 cases) and acute febrile disease (33 cases). The patients' age ranged from 1 to 89 years (mean 51.1 years). The most frequent clinical manifestations were: fever (95.7% of cases), cephalalgia (92.6%), stiffness of the neck (89.1%), vomiting (62.5%), marked asthenia (46.5%), myalgia (28.9%). In addition, patients with encephalitis exhibited: alteration of consciousness (89.2% of cases), tremor of extremities (40.4%), ataxia (44%), paralysis (15.1%). The fatality rate was 15.1% in acute encephalitis, 1.8% in acute meningitis and 0% in the acute febrile disease.

Particular features of clinical pellagra.

The follow-up of an important number of patients during the last three decades has shown a substantial difference between the clinical description of pellagra in the 40's (the triad: dermatitis, diarrhea, dementia) and its clinical aspects today: sun-exposed teguments revealing erythema and rapidly becoming pigmented and parchment like, dried, parched lips, angular stomatitis, lead like sclera fine cornea vascularization; gastro-intestinal disturbances: constipation, unjustified diarrhea, strange migratory abdominal feelings accompanied by ubiquitous dysesthesias. Other characteristics of this form of disease are: unexpressive look, continuously concerned, thoughtful, anxious or frowning, labile mind, headaches, insomnia. Villager's neurosis sometimes may be considered, in an appropriate clinical context, as a facet of nutritional deficiency. It is considered that the "classical" features of pellagra have changed due to: protein ingestion slightly below the lowest normal limit, decrease of strenuous physical activity and some associated diseases (frequently gastrointestinal disorders, chronic alcoholism).

Impaired glucose tolerance in the third trimester of pregnancy: associated factors to its persistence postpartum.

Glucose tolerance (75 g OGTT, according WHO) during the third trimester of pregnancy, in 302 women, has formerly been evaluated. Of these, 37 women were reinvestigated, with the same methodology, in absence of pregnancy and lactation, 2 years postpartum. According to oral glucose tolerance three groups were differentiated: group A (n = 14) with normal glucose tolerance (NGT) both in pregnancy and postpartum. Group B1 (n = 12) with impaired glucose tolerance (IGT) in pregnancy but NGT postpartum. Group B2 (n = 11) with IGT both in pregnancy and postpartum. B2 group had increased values (mean + SD) for age (37.0 +/- 6.6 years) versus B1 (30.2 +/- 5.5; p < 0.02) and A (29.5 +/- 5.9); p < 0.02) groups and BMI (32.5 +/- 4.2) versus 26.4 +/- 5.2; p < 0.01 and 23.3 +/- 4.4; p < 0.001 respectively). The ratio between basal insulinogenic indexes (microU IRI/mg BG) during pregnancy and 2 years postpartum has been significantly reduced in B1 (1.4 +/- 0.8) and B2 (1.5 +/- 0.6) as compared to A (2.5 +/- 1.1; p < 0.01) group suggesting, by comparison, the persistence of an increased level of insulin resistance postpartum in B1 and B2 groups. Insulinogenic index, after oral glucose was lower in B2 (34.4 +/- +/- 7.8) versus B1 (53.5 +/- 20.9; p < 0.01) group. These results suggest that, on an increased insulin resistance background, the decrease in glucose induced insulin response and increase in age and BMI are associated to deterioration of glucose tolerance early in the natural history of NIDDM.

Pancreatic B-cell culture after intravitam B-cell selection with nitric pilocarpine and modified B-technique use.

Our purpose was intravitam selection of endocrine pancreatic tissue. We decided to use 3% nitric pilocarpine as oral treatment for normal Wistar rats. This experiment was made on 12 male normal Wistar rats, 8 of them receiving 0.025 ml 3% nitric pilocarpine in a single daily dose, for 7 days. In the next 3-4 days, all of these have demonstrated clinical picture of exocrine pancreatic failure leading finally to death. Animals have received ad libitum food-intake. During this period, the study group has demonstrated glycemia values between 65...75 mg/dl vs. 68...85 mg/dl for normal group. The histological picture of study group's pancreatic pieces demonstrated intensive necrobiotic changes for exocrine components, but normal features for the exocrine ones. Furthermore we have obtained primary monolayer cultures of this dominant B-cell tissue, using a modified B-technique. Our results demonstrated the greatest percentage of B-cells on the cultures, in comparison with the non-using pilocarpine method (other studies). The presence of mega-beta-islet cells in primary cultures, as well as the lack of fibroblast population, demonstrated the efficiency of this method.

Effect of vitamin C administration on the ratio between the pro- and antioxidative factors.

Much evidence gathered in the last years involve the free radicals (FR) in the mechanisms of initiation, development of neoplastic transformations in vivo and in vitro, as well as in the activity of specific oncogenes. Most of it comes from the fact that the agents that remove the FR or interfere in the chain of events induced by FR can inhibit the neoplastic process both at cellular and molecular level. The antioxidant and free-radical scavenging activities of vitamin C have been intensely investigated, vitamin C being considered the most important antioxidant protective agent in the plasma. Our study is focused on the changes in lipid peroxides (MDA), free SH groups and the total antioxidative capacity in the plasma of 22 patients with differentiated thyroid cancer operated and treated with 131I, and then given 1 g vitamin C/day along one month. Blood samples were collected before 131I and then 4 days following 131I administration, and after 1 month of vitamin C administration per os. The following results were noted: (1) an increase of MDA concentration after 131I; (2) a decrease in the MDA level after one month of vitamin C administration; (3) an increase in the concentration of free SH groups after 131I; (4) a decrease in the level of free SH after vitamin C, and (5) a non-significant decrease in TAC after 131I and vitamin C. The results confirm the change in the balance between the oxidative and antioxidative factors under the effect of ionizing radiations and suggest the involvement of vitamin C as a protective and/or potentiating factor for the other antioxidative systems.

Oxidative and antioxidative factors in the serum of thyroid cancer patients treated with 131I.

The variation of some parameters involved in maintaining the balance between pro- and anti-oxidative factors was followed-up in a group of patients thyroidectomized for folliculo-papillary, papillary and follicular cancer, before and after 5 days following the 131I administration. Radiotherapy led to the intensification of lipid peroxidation expressed by a significant increase in the malondialdehyde values. Among the parameters involved in the antioxidative process we noted an increase in both SH nonprotein groups and ceruloplasmin concentration. The total antioxidative capacity lowered significantly following irradiation, whereas uric acid remained unaltered.

The role of free radicals in normal and pathologic cell proliferation.

Oxygen, while essential for life, is at the same time involved in the toxic effects of exposure to ionizing radiations, U.V. and a variety of chemical substances. All these cause an increased production of oxygen-derived free radicals (ODFR) and a modified pro-oxidant state. Many studies point to the involvement of the mechanisms controlled by ODFR in regulating the normal cell proliferation. In recent years, much evidence has been gathered implying the ODFR in the mechanisms of initiating and promoting the neoplastic transformations in vivo and in vitro, and in the activation of specific oncogenes.

A retrospective study on the treatment and evolution of Graves' ophthalmopathy.

Although Graves' ophthalmopathy (GO) seems to be unanimously considered as an autoimmune disease, its pathogenesis is still unknown. That is why the different therapeutical formulas led to ambiguous results. We think that a critical retrospective analysis on our therapeutical possibilities in GO will help us to become aware of our limits in treating this pathology. Our study performed on 123 patients with GO-stage III-IV who were admitted several times in the Thyroid Department of our Institute between 1975-1991; mean age 42 yrs (42 in men and 43 in women. One hundred and twelve patients presented GO associated with thyroid hyperfunction and 11 patients--with hypo- and euthyroidism. Thyroid status was evaluated through clinical examination and laboratory investigations (radioiodine uptake--RIU, 2h, 24 hrs, Achillean reflexogram--AR, T4, T3--radioimmunoassay-RIA). Three therapeutical formulas which were available to us were used in our subjects with GO: 1) general corticotherapy (C) was given in 77.6% of the cases; initial doses: 60-40 mg prednisone for 3 weeks followed by decreasing doses for 2 months (number of cures according to GO severity); 2) orbital radiotherapy (RT) alone was administered from the very beginning to the subjects in whom general C was not possible (7.4% of the cases); 3) general C associated with orbital RT were applied in the very severe cases of GO stage IV-VI (15% of the cases). The two available formulas acted particularly on oedematous symptoms (53% with C and 55.55% with RT alone). Muscular changes were improved by C in 30.83% and by RT only in 11.11% of the cases. It was noticed a mild positive effect on protrusion under C in only 11.66%, and under RT in 33% of the cases. The less favourable results in the cases under both C and RT can be explained by the fact that these groups included cases with stages IV-VI of GO with severe evolution. In 24% of the patients we noted an aggravation of the GO evolution regardless the therapy administered. The possible pathological relationship between the exophthalmic syndrome (ES) and hyperthyroidism (HT) is also supported by our data. The onset of ES together with HT occurred in 63% of the cases. On the other hand, we can notice that it was a more severe disease evolution when both ES and HT were associated. The treatment of hyperthyroidism led to GO aggravation (following 131I, thyroidectomy and antithyroid agents (ATD) in 43%, 52% and 29% of the cases, respectively).

A study on the types of diabetes mellitus in first degree relatives of diabetic patients.

The genetic characteristics of the diabetic types have been assessed by following up their frequency in first degree relatives of some non-selected diabetic patients, registered at eight different centers of the country. Out of 1,003 non-diabetic controls only 46 (4.6%) had 52 diabetic relatives, 65.4% of type 2 (non-insulin-dependent). Comparatively, out of the 704 patients, 172 (24.4%) had 229 diabetic first degree relatives, 72.5 of type 2. Out of 231 type 1 (insulin-dependent) diabetic patients, 29 (12.6%) had 34 diabetic relatives, 55.9% of type 1. Out of 300 type 2 patients, 99 (33.0%) had 121 diabetic relatives, 84.0% of type 2. The other 173 diabetic patients presented an "intermediary" type of the disease (needing insulin many years after onset). Forty-four (25.4%) of them had 64 diabetic relatives, 67.2% of type 2, 20.3% of type 1 and 12.5% with "intermediary" diabetes. The five times higher frequency of diabetes in patients' relatives versus controls is pointed out. Type 2 diabetic relatives predominated. The proportion of probands with diabetic relatives increased from 4.6% in non-diabetics to 12.6% in type 1, to 25.4% in "intermediary" diabetes and to 33.0% in type 2. The heredity of type 1 prevailed in type 1 and that of type 2 in type 2 and in "intermediary" diabetes. The fact that "intermediary" diabetes tends towards type 1 (insulin-dependent) as therapy and towards type 2 (non-insulin-dependent) as heredity might be an argument supporting the controversy on the diabetic syndrome classification.