Adequate Metabolic Control Research Articles

Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novelASLpseudogene

Argininosuccinic aciduria (ASAuria) is an inborn error of metabolism caused by mutations in the argininosuccinate lyase (ASL) gene, which leads to the accumulation of argininosuccinic acid (ASA) in body fluids and severe hyperammonemia. A severe neonatal form and a milder late-onset variant are described. We report a novel ASL pseudogene located in the centromeric region of chromosome 7, 14 novel mutations in the ASL gene, and a novel intronic polymorphism found in a cohort of Italian patients. Our approach relied exclusively on genomic DNA analysis. We found seven missense mutations, two nonsense, three small insertions/deletions, and two splicing mutations. Only two patients harbored previously described mutations, and among the novel variants only two were present in more than one kindred. The pathogenicity of the splicing mutations was demonstrated by a functional splicing assay that employed a hybrid minigene. We also performed molecular modeling using the reported three-dimensional structure of ASL to predict the functional consequences of the missense mutations. There was no genotype-phenotype correlation. Patients with neonatal onset display developmental delay and seizures despite adequate metabolic control. Moreover, hepatomegaly, fibrosis, and abnormal liver function tests are common complications in these patients, but not in patients with the late infancy form. We stress the importance of mutation analysis in patients with ASAuria, to confirm the clinical diagnosis, and to perform DNA-based prenatal diagnosis in future pregnancies of these families.

In Vitro TNF‐α and IL‐6 Production by Adherent Peripheral Blood Mononuclear Cells Obtained from Type 1 and Type 2 Diabetic Patients Evaluated according to the Metabolic Control

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were evaluated in lipopolysaccharide (LPS)-stimulated cell cultured monocytes obtained from 24 type 1 and type 2 diabetic patients presenting inadequate (IN) or adequate (AD) metabolic control, and in 21 healthy individuals paired to patients for sex and age. The TNF-alpha levels in stimulated cultures of diabetic patients were similar to healthy individuals, and type 1 diabetic patients showed increased IL-6 supernatant levels. The tendency toward increased TNF-alpha and IL-6 levels was observed with metabolic control of type 1 and type 2 diabetic patients, suggesting that the control of diabetes improves the capacity of activation and maintenance of the proinflammatory immune response.

Effect of metabolic control on the in vitro proliferation of peripheral blood mononuclear cells in type 1 and type 2 diabetic patients

Diabetes mellitus is a clinical syndrome that frequently leads to the development of chronic complications and high susceptibility to infections. It is probably due to defective immunological defense, which may be related to metabolic control of the disease. The aim of this study was to evaluate the effect of metabolic control on immune-cell behavior in type 1 and type 2 diabetic patients. For this, the in vitro proliferation of peripheral blood mononuclear cells (PBMC) was analyzed in patients with inadequate and adequate metabolic control. Experimental/laboratory study at a university hospital. Eleven type 1 and thirteen type 2 diabetic patients were studied, together with 21 healthy individuals divided in two groups (11/10), who were matched by sex and age with those diabetic patients. PBMC cultures stimulated with concanavalin-A (Con-A) were used to measure 3H-thymidine incorporation after 72 hours of cell culturing. For patients with inadequate metabolic control, culturing was performed on the first day of patient hospitalization and again after intensive treatment to achieve adequate control. The proliferation index for Con-A-stimulated cultures from type 1 diabetic patients was significantly greater than that for cultures from healthy individuals and type 2 diabetic patients, independent of metabolic control. A negative correlation between the proliferation cell index and body mass index and serum C-reactive protein levels was also observed. The increase in the proliferation capacity of type 1 diabetic T lymphocytes was probably not caused by hyperglycemia and/or insulinopenia related to inadequate metabolic control.

Behavioral Assessment and Intervention in Pediatric Diabetes

This article reviews the empirical research literature on behavioral assessment and intervention methods in the context of diabetes mellitus in children and adolescents. The review summarizes the pathophysiology, medical management, and monitoring of pediatric type 1 and type 2 diabetes. Next, the article describes common behavioral barriers to acceptable diabetes management and adequate metabolic control and the role of behavior change agents in evaluation and intervention for these problems. Validated approaches to the assessment of diabetes-specific behavioral problems are described for the measurement of treatment adherence, diabetes-related fears and avoidance behaviors, diabetes-specific social skills, and disease-related stressors. Behavioral interventions that have empirical support are discussed, including treatments that target treatment adherence, social skills, coping skills, family communication and problem solving, anxiety and stress management, and weight control. The article concludes with clinical practice recommendations for behavior change specialists who have the opportunity to work with this population.

A Practical Citrate Anticoagulation Continuous Venovenous Hemodiafiltration Protocol for Metabolic Control and High Solute Clearance

Obstacles to the widespread use of continuous renal replacement therapy (CRRT) include the need for anticoagulation, customized solutions, and complex protocols that carry an attendant risk for error, raise cost, and increase pharmacy and nursing workload. However, high solute clearance using CRRT with an effluent rate of 35 ml/kg per h has also recently been associated with improved survival in critically ill patients with acute renal failure. No published CRRT protocols using dilute regional citrate anticoagulation have achieved adequate metabolic control, effective anticoagulation, and high solute clearance in a practical, user-friendly, and economical manner. The safety and the efficacy of continuous venovenous hemodiafiltration at effluent rates of 35 ml/kg per h in critically ill acute renal failure patients were evaluated prospectively using a standardized bicarbonate-based dialysate; a systemic calcium infusion; and two separate trisodium citrate replacement solutions, a 0.67% solution and a 0.5% solution. All patients achieved adequate metabolic control, the desired effluent rate of 35 ml/kg per h, and high solute clearance. Use of the 0.67% citrate replacement solution resulted in mild alkalosis, whereas the 0.5% solution maintained appropriate acid-base balance. There was no difference in dialyzer survival between the 0.67 and 0.5% citrate groups (80 versus 82%; P = 0.60, Kaplan-Meier analysis). Dilute regional citrate as part of a CRRT protocol with a standard 25-mmol/L bicarbonate dialysate provides adequate metabolic control, high diffusive and convective clearance, and excellent dialyzer patency in a practical and cost-effective manner.

The hypothalamus–pituitary–ovary axis and type 1 diabetes mellitus: a mini review

A high prevalence of menstrual cycle and fertility disturbances has long been associated with diabetes mellitus. However, rationalization of the intrinsic mechanisms of these alterations is controversial and even contradictory. This review considers (i) the relationship between diabetes mellitus, especially type 1 diabetes mellitus (T1DM), and the hypothalamus-pituitary-ovary (HPO) axis, (ii) the state of our knowledge concerning neuroendocrine control and its relationship with dopaminergic and opioid tonus, and (iii) the influence of the hypothalamus-pituitary-adrenal axis on ovarian function. Functional disturbances that occur as a consequence of diabetes are also discussed, but some T1DM-related diseases of autoimmune origin, such as oophoritis, are not further analysed. Although there are clear indications of a relationship between menstrual and fertility alterations and glycaemic control, in many instances the improvement of the latter is not sufficient to reverse such alterations. It appears that the oligoamenorrhoea and amenorrhoea associated with T1DM is mainly of hypothalamic origin (i.e. failure of the GnRH pulse generator) and may be reversible. The importance of the evaluation of the HPO axis in T1DM women with menstrual irregularities, even in the presence of adequate metabolic control, is emphasized.

Prenatal and postnatal treatment in cobalamin C defect

To evaluate prenatal treatment with hydroxycobalamin (OH-Cbl) in a pregnancy at risk for a severe form of the cobalamin C defect and postnatal treatment of the affected child. Observational study with non-randomized intervention. In contrast to reported pregnancies with affected fetuses in which maternal methylmalonic aciduria was found in the last trimester of pregnancy, there was no maternal methylmalonic aciduria in our case, given prenatal treatment with intramuscular OH-Cbl. We did not find that the concentration of odd long-chain fatty acids in cord blood erythrocytes reflects fetal methylmalonic academia. After birth, the infant was treated with intramuscular OH-Cbl and oral carnitine. Oral folate and betaine were added as adjunct therapy to decrease plasma total homocysteine. Because of inadequate metabolic control, a diet reduced in natural protein was introduced. The child had normal developmental milestones but had nystagmus, hyperpigmented retinopathy, and discrete truncal muscular hypotonia. Despite prenatal and postnatal treatment, adequate metabolic control, absence of metabolic crises, and normal developmental milestones, this patient with the cobalamin C defect had characteristic symptoms of the disease.

Dermatoses em pacientes com diabetes mellitus

It is yet unknown the relationship between diabetes and determinants or triggering factors of skin lesions in diabetic patients. The purpose of the present study was to investigate the presence of unreported skin lesions in diabetic patients and their relationship with metabolic control of diabetes. A total of 403 diabetic patients, 31% type 1 and 69% type 2, underwent dermatological examination in an outpatient clinic of a university hospital. The endocrine-metabolic evaluation was carried out by an endocrinologist followed by the dermatological evaluation by a dermatologist. The metabolic control of 136 patients was evaluated using glycated hemoglobin. High number of dermophytosis (82.6%) followed by different types of skin lesions such as acne and actinic degeneration (66.7%), pyoderma (5%), cutaneous tumors (3%) and necrobiosis lipoidic (1%) were found. Among the most common skin lesions in diabetic patients, confirmed by histopathology, there were seen necrobiosis lipoidic (2 cases, 0.4%), diabetic dermopathy (5 cases, 1.2%) and foot ulcerations (3 cases, 0.7%). Glycated hemoglobin was 7.2% in both type 1 and 2 patients with adequate metabolic control and 11.9% and 12.7% in type 1 and 2 diabetic patients, respectively, with inadequate metabolic controls. A higher prevalence of dermatophytoses was seen in the both groups with inadequate metabolic control. The results showed a high prevalence of skin lesions in diabetic patients, especially dermatophytoses. Thus, poor metabolic control of diabetes increases patient's susceptibility to skin infections.

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

Insulin resistance is well recognized both in type 1 diabetes mellitus (T1DM) and in obesity. Studies concerning the relation between insulin resistance and overweight in T1DM have not yet been carried out. Degree of overweight [standard deviation score-body mass index (SDS-BMI)] and daily insulin doses per weight (ID/kg), per body surface (ID/m2), and per ideal body weight (ID/IW) were recorded in 4124 children aged between 5 and 20 yr with a duration of T1DM of 4-5 yr and an adequate metabolic control [hemoglobin A1c (HbA1c) <8.0%]. SDS-BMI was compared between insulin-resistant (ID/kg > or = 1.0) and insulin-sensitive (ID/kg <1.0) children. The ID/kg, ID/m2, and ID/IW were compared between obese (SDS-BMI >1.9) and non-obese children. Multivariate linear regression analysis was conducted for the dependent variables ID/kg, ID/m2, and ID/IW, including age, gender, SDS-BMI, and HbA1c as independent variables. The 882 insulin-resistant children did not differ significantly (p = 0.447) with respect to SDS-BMI (median +0.38) compared to the 3242 insulin-sensitive children (median SDS-BMI +0.42). The ID/kg was significantly (p = 0.031) lower in the obese children compared to the non-obese children (median 0.80 vs. 0.83), while ID/m2 (median 31.0 vs. 26.2) and ID/IW (median 1.17 vs. 0.85) were significantly (p < 0.001) increased in the obese children. In multivariate linear regression analysis, SDS-BMI was significantly (p < 0.001) associated with an increase in ID/m2 and ID/IW and a decrease in ID/kg. T1DM children with insulin resistance based on ID/kg are not more overweight than insulin-sensitive children with T1DM. ID/m2 and ID/IW seem to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1DM.

Oral Health Status in a Population of Nigerian Diabetics

Oral manifestations of diabetes mellitus have been documented, but the effect of glycemic control on the oral tissues has been scantily reported. The oral health status of 65 metabolically controlled adult diabetic patients attending the Diabetes Clinic of Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria, was prospectively assessed over six months and compared with that of 54 non-diabetic acting as controls. The mean duration of diabetes was 100.5+/-85.1 months. The difference in periodontal status of the patients and control, assessed using the Community Periodontal Index of Treatment Needs (CPITN), was not statistically significant (p=0.07). The degree of hyposalivation between the two groups was, however, statiscally significant (p<0.05). No significant difference was observed in the altered taste, burning mouth sensation, angular cheilitis, glossitis, and stomatitis status of the two groups. We conclude, with adequate metabolic control, the oral health status of a diabetic may not be significantly different from that of a non-diabetic except for xerostomia. A good understanding of the interactions between systemic diseases and oral health is imperative for physicians and dental practitioners. The need for early detection and closer linkages between the dental and medical professions in managing diabetic patients is emphasized.

Pregnancy in women with type 2 diabetes: an uncertain prognosis

The increasing prevalence of type 2 diabetes in women of childbearing age leads to an increasing number of pregnant women with type 2 diabetes. Pregnancy complicated by type 2 diabetes is a high-risk pregnancy, associated with birth defects and high perinatal mortality to the same extent as in type 1 diabetes. Until now, most attention was directed toward women with type 1 diabetes. Recent data stresses the urgent need to develop better screening and efficient care strategies in women with type 2 diabetes, who also display many risk factors for adverse fetal outcome. Family physicians, diabetologists and gynaecologists must be aware of this growing concern. Improvement of pregnancy planning, adequate metabolic control from conception to delivery and a multi-disciplinary team approach to care should improve fetal and maternal outcomes. Furthermore, diabetes screening in high-risk women prior to pregnancy is warranted.

Lipoatrophic Diabetes in an Elderly Woman: Clinical Course and Serum Adipocytokine Concentrations

Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology remains unknown. Pathophysiology of this disorder is characterized by generalized loss of body fat associated with an infrequent form of diabetes mellitus (lipoatrophic diabetes). Main features of this form of diabetes mellitus are the severe insulin resistance and the absence of ketoacidosis. Lipodystrophy can be congenital or acquired. In the acquired form, metabolic disturbances usually begin in the first years of life and the response to conventional treatment is very poor. Some alterations in serum adipocytokines have been described in this disease. We report the case of a 74-year-old woman with acquired generalized lipodystrophy who presented with low-normal serum concentrations of leptin, low adiponectin and resistin levels, and high serum levels of TNF alpha. Patient was initially treated with fenofibrate, metformin and high doses of subcutaneous insulin achieving an adequate metabolic control. During this period, serum adipocytokines were periodically measured. We comment on the different etiopathogenic mechanisms and the therapeutic modalities of this rare syndrome.

Changes in liver enzymes after clinical islet transplantation.

Clinical islet transplantation (ITx) shows insulin independence with adequate metabolic control in patients with type 1 diabetes. The aim of this study was to characterize the pattern of elevation in liver enzymes observed after ITx and to investigate any correlation between these elevations and graft characteristics or graft functional outcome. Eighty-four consecutive ITx procedures were performed in 42 recipients. Liver function tests (LFT) were assessed during the first 40 days posttransplant. LFT elevated greater than or equal to 2.5 times above the upper limit of normal (ULN) were considered relevant. In 54% of the transplants, the aspartate aminotransferase (AST) increased by more than 2.5 times above ULN. A 5-fold increase in AST was observed in 27% of the procedures. The highest AST levels were observed after the first ITx. AST for all transplants peaked at 7+/-0.5 days at a value of 162+/-23 U/L (P<0.001, compared with the pretransplant values). Changes in alanine aminotransferase were similar to AST. Alkaline phosphatase increased more than 2-fold above ULN in 12% of the procedures. LFT normalized in 90% of the recipients within 4 weeks posttransplant. The remaining 10% normalized within 2 months after ITx. Graft characteristics and graft function were not significantly different when comparing LFT with greater than 5-fold versus less than 2.5-fold increase above ULN. The mean bilirubin remained within the normal range. After intraportal ITx, a significant increase in LFT levels was noticed in more than 50% of the procedures. These levels normalized spontaneously in 90% of the recipients within 4 weeks. No correlation between the increase in LFT and graft characteristics or graft function was found.

Outcome of pregnancy among immigrant women with diabetes.

We studied outcome of pregnancy among immigrant women with diabetes. The women came from regions of the world with high incidence of impaired glucose tolerance and type 2 diabetes. Prevalences, secular trends, and sociodemographic risk factors of diabetes were also explored. Data from the Medical Birth Registry of Norway on all births from 1988 to 1998 for mothers born in South Asia and North Africa (11,268) and Norway (601,785) were analyzed. The prevalence of pregestational diabetes among the immigrants was 8.9/1,000 births, which was more than twice the rate among ethnic Norwegians (3.6/1,000). Time trends indicated increasing prevalences in both groups. Among the immigrants, diabetes was closely associated with maternal age. Maternal diabetes was associated with a significantly increased risk of pregnancy complications in both study groups. Increased risks were found for low birth weight, macrosomia, preterm birth, preeclampsia, and cesarean sections. Among ethnic Norwegians, maternal diabetes conferred a significantly increased risk of infant perinatal death (odds ratio 2.00, 95% CI 1,44-2.77). In the sample of immigrant women with predominantly type 2 diabetes, maternal diabetes was not significantly associated with perinatal death or congenital malformations in the offspring. The high prevalence of diabetes among immigrants from South Asia and North Africa represents a challenge for health care providers. To prevent adverse pregnancy outcomes and later cardiovascular and renal morbidity among these groups, early diagnosis of diabetes, adequate metabolic control, and relevant preventive measures are warranted.

Efecto del clorhidrato de metformina sobre el metabolismo en mujeres con síndrome de ovarios poliquísticos

The efficiency of the use of metformin chlorhydrate in patients with polycystic ovarian syndrome and history of infertility and menstrual disorders was evaluated in a double blinded, randomized, phase II clinical trial over a one year period at Camagüey Clinical- Surgical Teaching Hospital. The universe of study was constituted by 169 women who had previously received treatment with ovulation inductors for a period of one year or more. This universe was divided into a control group composed of 83 women treated with ovulation inductors (group I); and a group of 86 women (group II), to whom in addition to ovulation inductors, metformin chlorhydrate was administered. This last group of patients was randomly determined with the objective of avoiding associated risks. Data was processed using the SPSS statistical program for Windows. Results are expressed through frequency distribution and contigency tables. The predominant age group was 24-30 years in both groups I and II. At the onset of the study obese patients predominated in both groups. A significant progress was observed in the waist/hip index in patients that used metformin chlorhydrate, as well as a return to normalcy of the values of insulin in nearly all of these patients following the use of this product, in comparison to those of the control group. Considerable improvement was obtained in the values of the lipid profile in the control group; the state of insulin resistance improved to the point of total absence in patients treated with metformin clorhydrate. At the end of the study none of the group II patients continued with altered fasting blood sugar, although with respect to the glucose tolerance test there was no notable difference between the two groups. The use ofmetformin clorhydrate in association with the classical therapy in patients with polycystic ovarian syndrome is recommended for better results in the achievement of adequate metabolic control. Se realizó un ensayo clínico fase II, controlado, con asignación aleatoria, en dos ramas, donde se evaluó la eficacia del uso del clorhidrato de metformina en el tratamiento de las pacientes portadoras del síndrome de ovarios poliquísticos (SOP), con historia de infertilidad y trastornos menstruales en un período de un año en el Hospital ClínicoQuirúrgico de Camagüey. El estudio estuvo constituido por 169 mujeres que recibieron tratamiento con inductores de la ovulación (clomifeno y/o gonadotrofinas) por un período igual o mayor de un año. Las pacientes se dividieron en dos grupos, un grupo control integrado por 83 mujeres con tratamiento con inductores de la ovulación(grupo I), y otro, de 86 mujeres, al que, además, se administró clorhidrato de metformina (grupo II). Este último grupo se determinó de forma aleatoria con el objetivo de evitar riesgos. Los datos se procesaron mediante el sistema estadístico SPSS para Windows realizándose distribución de frecuencia y tablas de contingencia. El grupo de edad predominante fue elde entre 24 y 30 años en ambos grupos. En la evolución del índice de masa corporal de las pacientes, alinicio del estudio, observamos el predominio de lasobesas en ambos grupos. También observamos unprogreso significativo del índice cintura/cadera en lasque usaron clorhidrato de metformina. Después deutilizar este producto los valores de insulina se normalizaron en casi la totalidad de las pacientes a diferencia del grupo control. Se logró una mejoría considerable de los valores del perfil lipídico en el grupo control. El estado de insulinorresistencia mejoró en mayor medida en las pacientes tratadas con clorhidrato de metformina, hasta el punto de no existir. Al finalde la investigación ninguna paciente de este grupo siguió presentando alteración de la glucemia en ayunas, aunque con respecto a la prueba de tolerancia a la glucosa no existieron diferencias significativas entre ambos grupos. Es recomendable el uso del clorhidrato de metformina en asociación con la terapia clásica en las pacientes con SOP, en aras de lograr un adecuado control metabólico.

Dietary management for children and adolescents with diabetes mellitus: personal experience and recommendations.

Diet has traditionally played an important role in diabetic therapy. Over the years, various diets have been proposed, often without scientific evidence. One of the main errors was (is) to speculate that there exists a direct linear correlation between the injection of x units of insulin and the utilization of y grams of glucose. If this were true, one should give more insulin to practice physical activity. In reality, it is the reverse. Dietary recommendations issued over the last few years are the same for diabetic and non-diabetic individuals in order to avoid degenerative diseases. In many countries, the intake of fat is too high, and that of complex carbohydrates too low. The so-called 'Mediterranean diet', in combination with appropriate insulin therapy, may be optimal. This consists mainly of fiber-rich complex carbohydrates (grain), vegetables, fruits, fish, and olive oil. Explanations of this diet should focus on quality rather than quantity of foodstuffs, and should be given by a multidisciplinary team. Prescription of a highly rigid diet has proved ineffective in producing adequate metabolic control, and increases the risk of deviations from the diet. In our experience, the proper use of the two-injection regimen, in countries where the meal schedule allows correct allocation of diet, may lead to 'intensive conventional therapy' and good metabolic control. It is inadequate to systematically assign the multiple-insulin injection regimen to intensified insulin therapy, and the 'conventional' two-injection regimen to a non-intensified insulin therapy. The proper use of the basal-bolus regimen, with increased flexibility in daily life and dietary freedom, cannot always be applied successfully before adolescence. The adjustment of insulin dosage is more complicated than in the twice-daily injection regimen because dose alteration cannot be made only according to sliding scales based on the glycemia measured immediately before the insulin injection. The simplistic use of these non-physiological sliding scales is the main error in the multiple daily insulin injection regimen. The use of fast-acting insulin analogs in the basal-prandial regimen improves post-prandial glycemia at the expense of an increase in pre-prandial glucose levels, if the period between two meals, and therefore two injections, exceeds 3-4 hours, because of the short duration of action. If there are 4-6 or 7 hours between two meals, it is better to use a rapid-acting insulin. Avoid dogmatism--only objective results (good glycosylated hemoglobin and lipid levels, as well as good quality of life) are important.

Type 2 diabetes outcomes.

Type 2 diabetes outcomes.

Impact of different levels of carbohydrate intolerance on neonatal outcomes classically associated with gestational diabetes mellitus

Objetive: To compare the influence of different levels of carbohydrate intolerance on neonatal outcomes. Study design: The cohort constituted by the 1962 pregnant women screened for gestational diabetes who gave birth at the University Hospital of Granada (Spain) in the year 1995 was followed retrospectively. Women were classified into three groups: diagnosis of gestational diabetes, positive screen but non-gestational diabetes, and negative screen. Frequency of adverse newborn outcomes were quantified for each group and compared for statistical significance. Results: Gestational diabetes was associated with a greater incidence of high birth weight, hypoglycemia and hypocalcemia. Adequate metabolic control of the illness reduced the risk of adverse outcomes. Birth weight traced a positive slope with respect to the degree of carbohydrate intolerance. Regardless of carbohydrate intolerance, macrosomia was always higher among gravidae with gestational diabetes risk factors than among women without them. Conclusion: Both maternal gestational diabetes risk factors and greater carbohydrate intolerance in gravidae are associated with an increase in adverse newborn outcomes.

Метаболизм андрогенов у мужчин, больных сахарным диабетом типа 1

The purpose of this work was to study metabolism and peripheral blood content of the main adrenal and gonadal androgens (dehydroepiandrosterone (DHEA) and DHEA sulfate and testosterone, respectively) in men of different age treated by insulin. Thirty-five diabetics type I aged 15-52 years and 34 age-matched healthy controls were examined. The levels of DHEA and DHEA sulfate in the peripheral blood were decreased in the diabetics in comparison with healthy men, the differences being the most pronounced at the age of 15-45years. In parallel with this, hydrocortisone levels were increased in the patients. Opposite changes in the levels of adrenal androgens and hydrocortisone cause a drastic shift in these hormones balance in the patients with type I diabetes. The content of testosterone was normal (20.6 ± 1.2 nmol/liter) in 28 of 35patients during insulin therapy, while in 7 with higher glycaemia values the mean testosterone content was no higher than 6.3 + 1.1 nmol/liter. Presumably, the content of testosterone remains normal in diabetics during insulin therapy in the presence of adequate metabolic control, while the content of adrenal androgens decreases

Prevalence of diastolic dysfunction in normotensive, asymptomatic patients with well-controlled type 2 diabetes mellitus

To evaluate the prevalence of left ventricular (LV) diastolic dysfunction in patients with type 2 diabetes mellitus free of cardiovascular disease, we studied 86 normotensive men and women (mean age 46 ± 6 years) with Doppler echocardiography. All subjects were asymptomatic for ischemic heart disease or heart failure. The traditional transmitral filling patterns were used to characterize diastolic physiology. The Valsalva maneuver was used to differentiate normal from pseudonormal LV filling pattern. All patients had a normal electrocardiogram at rest and a negative result on exercise echocardiography for inducible wall motion abnormalities. Global LV systolic function was normal (mean LV ejection fraction 58%, range 53% to 76%). Diastolic dysfunction was found in 41 subjects (47%) of which 26 (30%) had impaired relaxation and 15 (17%) had a pseudonormal filling pattern. The mean LV mass index was 101 g/m 2 (range 86 to 122). All patients with a normal-filling physiology had gender-adjusted normal LV mass index (mean 93 ± 11 g/m 2), whereas 62% of those with either abnormal relaxation (mean 103 ± 12 g/m 2, p <0.001) or a pseudonormal pattern (mean 110 ± 12 g/m 2, p <0.001) had increased LV mass index. No subject in this cohort had restrictive diastolic physiology. In conclusion, diastolic dysfunction in type 2 diabetes mellitus patients is often found despite adequate metabolic control and freedom from clinically detectable heart disease. The Valsalva maneuver can unmask an additional 17% of patients with subclinical abnormal LV filling pattern, who otherwise would be classified as having a normal diastolic physiology. Increased LV mass index is closely associated with abnormal LV filling characteristics.