IGF-2 INDUCED HYPOGLYCEMIA ASSOCIATED WITH LUNG SARCOMA.

Hypoglycemia from a non-insulin-secreting extrapancreatic tumor is a paraneoplastic syndrome characterized by the tumor production of a substance with an insulin-like effect (insulin-like growth factor 1 or 2 - IGF 1 or 2). Diagnosis is confirmed by the determination of IGF-1 and IGF-2 and finding an elevated IGF - 2/IGF-1 ratio. The availability of these tests is limited in many laboratories, so prompt recognition and therapies are late. We present the case of a 70-year-old patient diagnosed with right lower lobe bronchopulmonary neoplasm who presented to the emergency department with an altered general condition and hypoglycemic coma. The evaluation revealed low levels of insulin and C-peptide along with an elevated IGF-2/IGF-1 ratio of more than 10, suggesting a diagnosis of lung sarcoma with production of IGF-2. Because the tumor could not be resected in this case, chemotherapy and radiotherapy were performed, along with glucocorticoid therapy to prevent recurrent hypoglycemia. In the case of a patient with lung sarcoma and recurrent hypoglycemia (especially severe hypoglycemia or coma), extrapancreatic non-hyperinsulinemic hypoglycemia should be determinate tumor IGF-2 secretion.

INSULIN AUTOIMMUNE SYNDROME IN A YOUNG CAUCASIAN WOMAN.

A young Caucasian woman presents several episodes of severe fasting hypoglycemia. Fasting lab tests revealed: glycemia 28 mg/dL, insulinemia 143.3 µU/mL, insulin antibodies above 100 U/mL, leading to the diagnosis of insulin autoimmune syndrome. Due to lack of clinical improvement after 2 months, prednisone was started at 0.5 mg/kg/day, and then tapered by 5 mg every 5 days. Three weeks after discontinuing corticotherapy, the patient had no more severe fasting hypoglycemia, but occasionally postprandial mild hypoglycemia. Fasting lab tests showed: glycemia 83 mg/dL, insulinemia 58.6 µU/mL. At 5 hours during oral glucose tolerance test glycemia was 33 mg/dL, insulinemia 152.9 µU/mL.

DIETARY PATTERNS AND THEIR ASSOCIATION WITH OBESITY: A CROSS-SECTIONAL STUDY.

CONTEXT: Scarce data on dietary habits in Eastern European countries is available and reports investigated individual food items and not dietary patterns in these populations. OBJECTIVE: To identify dietary patterns and to explore their association with obesity in a sample from Romanian population. DESIGN: Cross-sectional. SUBJECTS AND METHODS: This was an analysis of data collected from 1398 adult participants in ORO study. Data on lifestyle, eating habits and food frequency consumption were collected. RESULTS: By principal component analysis we identified 3 dietary patterns explaining 31.4% of the diet variation: High meat/High fat pattern, Western pattern and Prudent pattern. High meat/High fat pattern was associated with male gender, lower educational level, living in a rural, smoking and a higher probability for the presence of obesity (OR 1.2 [95%CI: 1.1-1.4]). Western pattern was associated with younger age, a higher level of physical activity and smoking. Prudent pattern was associated with older age, female gender, a higher level of physical activity, not smoking status and a lower probability for the presence of obesity (OR 0.8 [95%CI: 0.7-0.9]). CONCLUSIONS: This study provides for the first-time information on the association between dietary patterns in adults from an Eastern European country and the presence of obesity.

NON-INVASIVE ASSESSMENT OF LIVER STEATOSIS AND FIBROSIS USING TRANSIENT ELASTOGRAPHY AND CONTROLLED ATTENUATION PARAMETER IN TYPE 2 DIABETES PATIENTS.

CONTEXT: Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. OBJECTIVE: To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. DESIGN: This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital "Pius Brinzeu" Timisoara. SUBJECTS AND METHODS: We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. RESULTS: The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). CONCLUSIONS: Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

Prevalence of overweight/obesity, abdominal obesity and metabolic syndrome and atypical cardiometabolic phenotypes in the adult Romanian population: PREDATORR study.

PURPOSE: The objectives were to assess the prevalence of overweight/obesity, abdominal obesity and metabolic syndrome (MetS), and to evaluate the characteristics of the metabolically unhealthy lean (MUHL) and metabolically healthy overweight/obese (MHO) phenotypes in a Romanian population-based sample from the PREDATORR study. METHODS: PREDATORR was an epidemiological study with a stratified, cross-sectional, cluster random sampling design. Participants were classified into four cardiometabolic phenotypes based on the BMI, the cut-off value being 25 kg/m(2), and the presence of MetS (defined according to the Harmonization definition 2009): MUHL, MHO, metabolically healthy lean (MHL) and metabolically unhealthy overweight/obese (MUHO). RESULTS: Overall, 2681 subjects aged 20-79 years were included in the analysis. The overall age and sex-adjusted prevalence of obesity was 31.90 %, overweight was 34.7 %, abdominal obesity was 73.90 % and MetS was 38.50 %. The age- and sex-adjusted prevalence of MHO phenotype was 31.60 %, while MUHL phenotype prevalence was 3.90 %. MUHL and MHO participants had a cardiometabolic profile, kidney function and CVD risk intermediary between MHL and MUHO. MUHL had higher odds of being associated with CVD risk (OR 5.8; p < 0.001), abdominal obesity, prediabetes, diabetes, hypertriglyceridemia and hypo-HDL cholesterolemia than MHL, while MHO phenotype was associated with hypo-HDL cholesterolemia (OR 3.1; p = 0.002), prediabetes (OR 2.9; p < 0.001) and abdominal obesity. CONCLUSIONS: PREDATORR study showed a high prevalence of obesity/overweight, abdominal obesity and MetS in the adult Romanian population, and their association with kidney function and several cardiometabolic factors.

CHOICE OF THE ADD-ON THERAPY TO METFORMIN IN TYPE 2 DIABETES PATIENTS IN CLINICAL PRACTICE. INITIAL RESULTS FROM A NON-INTERVENTIONAL MULTICENTER STUDY IN ROMANIA (REALITY).

Metformin, a biguanide, remains the most widely used first-line type 2 diabetes drug. It is generally considered weight-neutral with chronic use and does not increase the risk of hypoglycaemia. Most patients eventually require more than one antihyperglycemic agent to achieve target blood glucose levels. The primary objective of this non-interventional study was to describe and compare the main criteria used by physicians from regular outpatient setting in selecting the add-on therapy in patients with inadequately metformin-controlled type 2 diabetes in 2 time points at 1-year distance by assessment of patient, and/or agent characteristics and/or physician decision. At the end of phase one of the study, the mean duration of type 2 diabetes was 6.8 years. The majority of patients included in the study were overweight (32%) and obese (62%), and presented diabetes complications (59.6%). In 50% of the cases, the major reason for selecting the second-line therapy was related to patient characteristics, while agent characteristics and physician decision were the main categories in 38% and 12%, respectively. Importance to achieve glycemic control and estimated treatment efficacy were selected in 73.9% and 82.4% of patients, calculated as percentage in the respective categories.

Chronic Kidney Disease--Chronic Liver Disease. An Immunologic Cross-talk.

The relationship between the kidney and other organs is notable. The best known is the relation with the cardiovascular system. Relationships with other organs are less studied, although their involvement sometimes dominates the clinical picture and the outcome of disease. The paper analyzes the kidney-liver relationship, namely chronic kidney disease and chronic liver disease from an immune viewpoint. The immune system operates as a unitary whole. There is an interdependence between the immune system of the liver, considered a lymphoid organ, and the kidney, whose participation in immune processes is well-known. The most important chronic liver diseases are viral hepatitis B and C. Infection with these viruses can lead to renal involvement, producing mainly glomerular disease. At the same time, secondary glomerulonephritis can cause an unfavorable outcome of the primary disease. The relationship between chronic liver disease and chronic kidney disease during chronic B and C hepatitis occurs via circulating immune complexes or complexes formed in situ. Cell-mediated immunity is also involved. The antiviral treatment of B and C hepatitis is also aimed at secondary glomerular disease. The participation of immune mechanisms raises the question of administering immunomodulating medication, a type of medication that influences viral replication--this is why it is associated with antiviral medication. Other two chronic liver diseases, namely liver cirrhosis, in which the main mechanism is a toxic one, and non-alcoholic steatohepatitis can produce via immune mechanisms glomerular involvement. In its turn, chronic kidney disease in advanced stages causes lipid metabolism disturbances with hypertriglyceridemia, which can influence fatty loading of the liver in the above-mentioned liver diseases. One can speak about a cross-talk between the liver and the kidney, in which immune mechanisms play an important role.

Polyphenols-rich natural products for treatment of diabetes.

Currently, experimental and clinical evidences showed that polyphenols-rich natural products, like nutraceuticals and food supplements, may offer unique treatment modalities in type 2 diabetes mellitus (DM), due to their biological properties. Natural products modulate the carbohydrate metabolism by various mechanisms, such as restoring beta-cells integrity and physiology, enhancing insulin releasing activity, and the glucose using. Sea buckthorn berries, red grapes, bilberries, chokeberries and popular drinks like cocoa, coffee and green tea are all rich in polyphenols and may decrease the insulin response, offer in g a natural alternative of treatment in diabetes. Therefore, researches are now focused on potential efficacies of different types of polyphenols, including flavonoids, phenolic acids, lignans, anthocyans and stilbenes. Animal and human studies showed that polyphenols modulate carbohydrate and lipid metabolism, decrease glycemia and insulin resistance, increase lipid metabolism and optimize oxidative stress and inflammatory processes. It is important to understand the proper dose and duration of supplementation with polyphenols-rich extracts in order to guide effective therapeutic interventions in diabetic patients.

Impact of gender and dialysis modality on early mortality risk in diabetic ESRD patients: data from a large single center cohort.

BACKGROUND: Diabetes mellitus (DM)-associated chronic kidney disease (diabetic renal disease) became the predominant etiology of the end-stage renal disease (ESRD) in the western countries and shows the same trend in the developing countries. Early mortality (EM) after the dialysis initiation, defined as death of all causes within the first 3 months after initiation of renal replacement therapy (RRT), is of concern especially for the high-risk renal patients including diabetics. The goal of the present study was to identify demographic and clinical risk factors associated with EM in a retrospective cohort of Romanian DM patients initiated on dialysis. METHODS: A retrospective case-control study was designed. Clinical recordings from all patients initiated on hemodialysis (HD) or peritoneal dialysis between January 1996 and December 2005 in the Dialysis Center of NIDNMD Paulescu, Bucharest, were collected and analyzed. Patients were classified accordingly in two groups: those who displayed EM formed the "cases" group, while the others were included in the "controls" group. Both univariate (subgroup analysis) and multivariate analyses (logistic regression, Cox regression) were used to analyze the impact of risk factors on EM outcome. RESULTS: Data from 788 patients were included in the analysis. The factors significantly associated with EM in the univariate analysis were female gender, late initiation (LI) of dialysis, old age and HD used as the first/only method. Applying the multivariate analysis, only the use of HD (OR = 4.20, p < 0.0001) and the LI of dialysis (p < 0.0001; 95 % CI 1.36-2.30) were associated with EM, while female gender showed only a trend to a higher EM (OR = 1.29, p = 0.052). CONCLUSIONS: Hemodialysis used as a first/single method for RRT and the LI of dialysis were independent predictors of EM in our ESRD diabetic patients. A possible explanation for the first factor could be our specific center procedure, which allows only the HD as rescue therapy method for the most severe cases, managed in the intensive care unit.

The solitary kidney--a nephrological perspective.

The solitary kidney (SK) is of special interest for practitioners because of the reduced number of nephrons as compared to persons who have 2 kidneys. It undergoes adaptive phenomena of hypertrophy and hyperfiltration that allow long-term evolution, but pathological situations might occur in the remnant kidney. In some persons with a SK, the adaptive phenomena can be associated with proteinuria, arterial hypertension (AH) and diminished Glomerular Filtration Rate (GFR). In very rare situations, diminution of renal function in patients with a SK can progress to end-stage renal disease (ESRD) and, totally exceptionally, it requires renal replacement therapy. The SK can be congenital or acquired. At present patients with a SK address themselves more and more frequently to nephrology services which monitor the evolution of both the congenital and the surgically acquired SK. The congenital SK possesses a higher number of nephrons (75%, as compared to 2 functional kidneys in a healthy person) than the surgically acquired SK - 50% nephrons. This makes adaptive phenomena differ. Secondary lesions sometimes appear later in case of the congenital SK. In other situations, no significant differences between the evolution of the congenital or acquired SK are registered. The congenital solitary kidney is often associated with congenital abnormalities of the kidney and of the urinary tract (CAKUT). This association increases the risk for chronic kidney disease and for evolution towards chronic renal failure. The congenital SK is also often associated with gynaecological and other abnormalities. The acquired solitary kidney can be due to nephrectomy on a pathological kidney which could not be conservatively treated or due to donation of a kidney for renal transplantation. The SK itself sometimes requires partial nephrectomy intervention, for example sparing surgery. Although the evolution is in most cases favorable, it requires attentive monitoring.

Aspects of renal function in patients with colorectal cancer in a gastroenterology clinic of a county hospital in Western Romania.

Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.

Biomarkers in assessing tubular lesions of the solitary kidney. The solitary kidney in special conditions.

The paper highlights the importance of tubular lesions of the solitary kidney (SK), identified and monitored by means of urinary biomarkers, mainly N-acetyl-beta-D-glucosaminidase (NAG), albumin, alpha 1-, and beta 2-microglobulin. It is considered that the assessment of a SK should be performed with four and not three parameters as it was usually done until recently: renal function, proteinuria and blood pressure (BP), to which biomarkers should be added. The solitary kidney can result after nephrectomy for kidney transplantation. In some countries living kidney donors represent the only option for performing kidney transplantation. The SK in living donors has generally a good evolution, although sometimes renal injury manifested by proteinuria, arterial hypertension (AH), or diminution of renal function does occur. Therefore, living donors require attentive monitoring. The SK is considered to have a good evolution (even in donors), in spite of alterations of the above-mentioned clinical and biological parameters. The very infrequent cases who evolve progressively towards renal failure are not predictable, which requires monitoring of all persons with a SK. The SK represents a special situation in case of association with a disease affecting the kidney, such as urinary tract infection (UTI), diabetes mellitus, or systemic lupus erythematosus (SLE). Pregnancy occurring in a person with a SK also needs attentive follow-up. Pregnancy associated diseases, such as preeclampsia occurring in patients with a SK, impose appropriate therapeutic behaviour. The SK remains a particular entity in nephrology which needs to be carefully monitored.

Diabetic nephropathy and multiorgan protection. Part II.

Diabetic nephropathy (DN) presents a complex pathogenesis in which both the vascular system and the metabolism, in its complexity and mainly glucidic metabolism, are involved. Together with the glucid metabolism, lipid metabolism, anemia, oxidative stress, generalised inflammation, vitamin D disorders and smoking participate in DN pathogenesis. All these factors that disturb the homeostasis of the patient with DN require protective factors which will be presented in the second part of the paper. Like hypotensive medication, and especially the inhibitors of the renin angiotensin aldosterone (RAAS) system, antiproteinuric medication, and especially intensive control of glycaemia that have an important protective role, the pathogenic factors mentioned above also require protective measures. As they interest the whole organism in DN and in DM, respectively, we speak about multiple organ protection or multiorgan protection. The concept of multiorgan protection is especially important in DM. Although sometimes, some measures with multiorgan protective character are applied in current practice, it is necessary that they should be gathered and applied within a well established framework, a fact that is achieved by the concept of multiorganprotection. Diabetes mellitus, requires multiple measures of protection because of its vascular and metabolic complications. Diabetic nephropathy represents an important complication of diabetes mellitus, frequently associated with its other complications. The first part of the paper presented the concept of multiorgan protection, as well as some of the main protective measures: control of blood pressure mainly by means of inhibitors of the renine angiotensine aldosterone system, glycaemia monitoring and antiproteinuric treatment. The second part of the paper refers to protective measures used in diabetes mellitus, and diabetic nephropathy, respectively, regarding control of the anaemia, of endothelial disturbances, of the metabolism of lipids, of oxidative stress, of inflammation, smoking, of the metabolism of vitamin D, respectively. Diabetic nephropathy, by the complexity of its lesions, as well as by the complications of diabetes mellitus, cannot be regarded as separate from the organism seen as a unitary whole, a reason because of which the measures of protection are not limited only to the kidney, they must address all organs and metabolism in general, requiring measures of multiorgan protection.

Diabetic nephropathy and multiorgan protection. Part I.

Diabetic nephropathy, one of the most important complications of diabetes mellitus, requires during its evolution protective measures defined as renoprotective. Since the complications of diabetes mellitus are not limited to diabetic nephropathy and as this is frequently associated with heart complications that require protective measures defined as cardioprotective, neurologic measures that require neuroprotection of the retina, of the large vessels etc., much more complex protective measures are necessary. The metabolic complications that are usually at the basis of the other complications at the level of the cell also impose measures of protection. Such an approach can have important practical consequences. It is a well-known fact that most patients with chronic kidney disease--CKD--do not reach final stages as in the meantime they decease because of cardiovascular diseases. Consequently, cardioprotective measures have to be associated with renoprotective ones, as well as protective measures that address other organs, in close connection with protective measures at metabolic level. The protective measures must also address to microcirculation, diabetic nephropathy being a disease that primarily affects microcirculation. Diabetes mellitus also frequently affects the large vessels, the circulatory system being usually affected in its complexity. The paper represents a synthesis of multiorganprotective measures in diabetic nephropathy, in diabetes mellitus, respectively, the concept of multiorgan protection finding in this disease an ideal domain of expression. The first part gives the main multiorgan measures: monitoring of blood pressure and, mainly, protection by means of the renine aldosterone (RAAS) system, multiorgan by intensive monitoring of glycaemia and by treatment of proteinuria. The second part presents the other protective measures used in diabetic nephropathy.

[Postoperative complete abdominal dehiscence: risk factors and clinical correlations]. / Evisceratiile postoperatorii: factori de rise ssi corelattii clinice.

UNLABELLED: The purpose of this study is to review our clinical experience with abdominal wound dehiscence in the Surgical Department of City Hospital Timisoara. PATIENTS AND METHODS: 19.116 abdominal procedures were performed between January 1992 - March 2009 in our Department and 29 complete dehiscences were identified (0,15%). Significant risk factors in our analysis were intraabdominal infection, wound infection, emergency surgery, malignancies, digestive fistulae, hiperabdominal pressure, sex and age over 65 years. Less significant factors were the abdominal type of incision, the method of wound closure and heart or respiratory diseases. CONCLUSIONS: postoperative complete dehiscence is a constant presence in a surgical department; despite its low frequency, wound dehiscence is associate with a hight mortality and morbidity rate, and increase the costs and hospitalisation periode. Risk factors evaluation and their associations represente an important role in the therapeutic management of the surgical patient.

The value of basal C peptide and its relationship with pancreatic autoantibodies in young adults with type 2 diabetes mellitus.

UNLABELLED: It is well known that sometimes it is difficult to distinguish between type 1 and 2 diabetes mellitus using clinical criteria, in subjects with disease onset relatively early in adult life. The measurement of C peptide level and of immunological markers may represent important additional tools for establishing the correct diagnosis. The aim of the study is to assess the trend of basal C peptide in patients with clinical diagnosis of type 2 diabetes and to relate it to the type of treatment, the body weight and the positivity for pancreatic autoantibodies. PATIENTS AND METHOD: we studied a group of 268 patients with type 2 diabetes, aged between 30 and 50 years, with a diabetes duration of less than 5 years. In all patients, we measured basal C peptide, islet cell autoantibodies and antibodies against glutamic acid decarboxylase, computed the body mass index and recorded the current antidiabetic treatment. RESULTS: Based on basal C peptide value, diabetic subjects fell under 3 categories: a) low C peptide (<0.58 ng/ml): 7.5%, b) normal C peptide (0.58-2.70 ng/ml): 57.8%, and c) high C peptide (>2.70 ng/ml): 34.7%. Patients with low C peptide were treated more often with insulin, while those in high C peptide group received more often biguanides. A direct correlation between C peptide and body weight was established. Mean C peptide was lower in patients positive for at least one pancreatic autoantibody, compared to those who were negative for antibodies CONCLUSION: Low basal C peptide can be considered criterion for transferring the patients, initially diagnosed as type 2 diabetes, in the type 1 diabetes group.

The epidemiology of childhood-onset type 1 diabetes mellitus in Romania. ONROCAD Study Group. National Romanian Organisation for the Care of Diabetic Children and Adolescents.

The ONROCAD Study group was established to provide descriptive epidemiological information on type 1 diabetes mellitus (DM) in Romania. Data on all new patients with type 1 DM with onset before age 15 years during the four-year period 1992-1995 in Romania were submitted from all members of the ONROCAD Study Group, representing all doctors and clinics that manage children with DM in Romania. Age- and sex-specific incidence rates were estimated, using available demographic data. A total of 706 new patients with type 1 DM and onset 0-14 years was registered. The overall completeness of ascertainment was estimated at 93.5%. For all Romania, the incidence of childhood-onset type 1 DM was estimated at 3.57/100,000/year. The incidence in the three regions was statistically significantly different (p = 0.002), with high rates in Transylvania and low rates in Muntenia. Girls had a significantly higher incidence than boys for each of the age groups 0-4, 5-9 and 10-14 years. Between these age groups, the incidence increased significantly with age. The incidence of childhood-onset type 1 DM is among the lowest recorded in Europe. Significant, but unexplained, geographical variation exists within Romania. Searches for factors to explain this heterogeneity may provide clues to the etiology of childhood-onset type 1 DM.