Role of the mitochondrial m.16189T>C variant in type 2 diabetes mellitus in southern Brazil.
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Brazil↗
Biomedical subjects
J L Gross
Publications and source records attributed to J L Gross.
The European-specific mitochondrial cluster J/T could confer an increased risk of insulin-resistance and type 2 diabetes: an analysis of the m.4216T > C and m.4917A > G variants.
The aims of this study were to investigate the contributions of the mitochondrial DNA m.4216T > C and m.4917A > G variants, and also of the European-specific mitochondrial cluster J/T, to the development of type 2 diabetes mellitus in Caucasian-Brazilian patients from Southern Brazil. We analyzed 347 type 2 diabetes patients and 350 control subjects. Variant frequencies in patients and control subjects were compared using chi2 tests or odds ratio. We also compared clinical and laboratory characteristics among patients with and without the variants. We found that the frequencies of the m.4216T > C and m.4917A > G variants are higher in diabetic patients than in control subjects. Moreover, haplogroups J (partially defined by the presence of the m.4216T > C variant only) and T (partially defined by the presence of both m.4216T > C and m.4917A > G variants) are more frequent in the type 2 diabetic group than in the control group. Patients belonging to the cluster J/T are more insulin resistant than patients of other haplogroups. In conclusion, our results indicate the association of the cluster J/T (as suggested by analyses of the m.4216T > C and m.4917A > G variants) with insulin resistance and type 2 diabetes.
Brazil↗
Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes.
Diabetic retinopathy is one of the leading causes of blindness in working-age individuals. Diabetic patients with proteinuria or those on dialysis usually present severe forms of diabetic retinopathy, but the association of diabetic retinopathy with early stages of diabetic nephropathy has not been entirely established. A cross-sectional study was conducted on 1214 type 2 diabetic patients to determine whether microalbuminuria is associated with proliferative diabetic retinopathy in these patients. Patients were evaluated by direct and indirect ophthalmoscopy and grouped according to the presence or absence of proliferative diabetic retinopathy. The agreement of diabetic retinopathy classification performed by ophthalmoscopy and by stereoscopic color fundus photographs was 95.1% (kappa = 0.735; P < 0.001). Demographic information, smoking history, anthropometric and blood pressure measurements, glycemic and lipid profile, and urinary albumin were evaluated. On multiple regression analysis, diabetic nephropathy (OR = 5.18, 95% CI = 2.91-9.22, P < 0.001), insulin use (OR = 2.52, 95% CI = 1.47-4.31, P = 0.001) and diabetes duration (OR = 1.04, 95% CI = 1.01-1.07, P = 0.011) were positively associated with proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95% CI = 0.86-0.96, P < 0.001) was negatively associated with it. When patients with macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95% CI = 1.56-6.98, P = 0.002) remained associated with proliferative diabetic retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic retinopathy more often presented renal involvement, including urinary albumin excretion within the microalbuminuria range. Therefore, all patients with proliferative diabetic retinopathy should undergo an evaluation of renal function including urinary albumin measurements.
Albuminuria↗
The Ala45Thr polymorphism of NEUROD1 is associated with type 1 diabetes in Brazilian women.
BACKGROUND: NEUROD1 encodes a transcription factor expressed in the endocrine pancreas, and involved in beta-cell development, function and mechanisms of apoptosis. In this study, we investigated the association of a frequent polymorphism in exon 2 of NEUROD1 (G > A; Ala45Thr) with Type 1 diabetes in Brazilian subjects. METHODS: A population/association study comprising 246 unrelated Type 1 diabetic and 275 nondiabetic white Brazilian subjects. The Ala45Thr variant was genotyped by a PCR-RFLP method. RESULTS: The frequency of the Thr allele was significantly higher in patients with Type 1 diabetes than in controls (42.3% vs 35.3%, P=0.02). Stratification by gender showed that homozygosity for the Thr allele was associated with Type 1 diabetes in women with odds ratio of 3.66 (95% C.I. 1.43-10.11, P=0.009) as compared to homozygosity for the Ala allele. This effect was not observed in men. CONCLUSIONS: We found a gender-specific association of the Ala45Thr variant of NEUROD1 with Type 1 diabetes in Brazilian women. Our results suggest that gender as well as ethnicity might modulate the association of NEUROD1 with Type 1 diabetes.
Alanine↗
High prevalence of extrathyroid malformations in a cohort of Brazilian patients with permanent primary congenital hypothyroidism.
The objective of this study was to evaluate the prevalence of major congenital malformations in a cohort of children with permanent primary congenital hypothyroidism (PCH). This cross-sectional study was conducted in 76 consecutive, unselected children with PCH recruited from a district hospital outpatient clinic. Malformations were identified by clinical examination. The prevalence of major congenital malformations in these patients was compared with the prevalence of malformations in children born at Hospital de Clínicas de Porto Alegre (HCPA). The etiology of hypothyroidism was established by scintigraphy and ultrasonography. Hypothyroidism was caused by thyroid dysgenesis in 67 patients (one case of hemiagenesis, 24 of ectopia, and 42 of agenesis); the gland was normally located and shaped in nine patients. Ten patients (13.2%) had major congenital malformations (1,316/10,000 patients), mostly cardiac. Malformations were observed only in patients with dysgenesis: thyroid agenesis (n = 7) and sub-lingual ectopic thyroid (n = 3). The prevalence of malformations was significantly higher (RR = 2.6; CI 95%: 1.3-4.8; p = 0.005) in this group than in HCPA newborns (509/10,000 patients). In conclusion, a high rate of extrathyroid congenital malformations, mostly cardiac, was found for patients with permanent PCH, especially thyroid dysgenesis. The present data support the existence of an association between CH and increased prevalence of congenital malformations.
Brazil↗
The presence of allele D of angiotensin-converting enzyme polymorphism is associated with diabetic nephropathy in patients with less than 10 years duration of Type 2 diabetes.
AIM: To investigate the association between angiotensin-converting enzyme gene I/D polymorphism and diabetic nephropathy (DN) in patients with Type 2 diabetes mellitus (DM) taking into consideration the known duration of DM. METHODS: Cross-sectional study with 982 patients categorized according to urinary albumin excretion (UAE) into normoalbuminuria (UAE < 20 microg/min or < 17 mg/l, 24-h timed urine or spot random sterile urine, respectively), incipient DN (UAE 20-199 microg/min or 17-174 mg/l) and overt DN (UAE > 200 microg/min or > 174 mg/l or dialysis). Patients were further grouped regarding presence of the D allele (DD/ID vs. II) and DM duration (< or = 10 years or > 10 years). RESULTS: Incipient DN was diagnosed in 17.3% (n = 170), and 20.7% (n = 203) had overt DN (macroalbuminuria, n = 129; dialysis, n = 74). Genotype distribution (DD/ID/II) was similar in patients with incipient (49/92/29) or overt DN (77/89/37) if compared with patients without DN (181/308/120, P = 0.172). In patients with DM < or = 10 years, having the D allele (DD/ID) resulted in an odds ratio (OR) of 2.66 (95% CI: 1.12-6.58, P = 0.015) for incipient DN, and 3.19 (95% CI: 1.18-9.30, P = 0.012) for overt DN. In patients with longer DM duration, the D allele did not increase the risk for incipient (OR 0.68, 95% CI 0.36-1.29, P = 0.206) or overt DN (OR 0.67, 95% CI 0.39-1.17, P = 0.138). CONCLUSION: The DD/ID genotypes were associated with incipient or overt DN in patients with DM < or = 10 years.
Albuminuria↗
The G1888A variant in the mitochondrial 16S rRNA gene may be associated with Type 2 diabetes in Caucasian-Brazilian patients from southern Brazil.
AIM: To compare the frequencies of the G1888A variant in the mitochondrial 16S rRNA gene between patients with Type 2 diabetes and non-diabetic control subjects from southern Brazil. METHODS: We analysed 520 Type 2 diabetic patients (389 Caucasian- and 131 African-Brazilians) and 530 control subjects (400 Caucasian- and 130 African-Brazilians). DNA samples were amplified by polymerase chain reaction and digested with the RsaI enzyme. Variant frequency in patients and control subjects was compared using chi2 test, Fisher's exact test or odds ratio test. We also investigated the frequency of the G1888A variant in a subgroup of the patients with a maternal history of Type 2 diabetes plus two or more features of maternally inherited diabetes and deafness. RESULTS: The 1888A allele does not seem to be associated with Type 2 diabetes in African-Brazilians (frequency of 3.8% in patients and 0.8% in control subjects; PFisher=0.213). However, in Caucasian-Brazilians, the 1888A allele was significantly associated with diabetes (12.3% in patients vs. 3.5% in control subjects; OR=3.881; 95% CI 2.106-7.164; P<0.001) and also with higher levels of insulin resistance. The majority of the patients carrying the 1888A allele did not have clinical features of maternally inherited diabetes and deafness. CONCLUSION: The present study indicates the association of the mitochondrial G1888A variant with Type 2 diabetes and insulin resistance in Caucasian-Brazilian patients from southern Brazil. However, further studies are required to confirm its effects on mitochondrial function and the role of these effects on the pathogenesis of Type 2 diabetes.
Aged↗
Predictors of intellectual outcome in a cohort of Brazilian children with congenital hypothyroidism.
OBJECTIVE: To identify predictors of intellectual development in a cohort of children with permanent primary congenital hypothyroidism. DESIGN: Cohort study with intellectual development as the outcome. PATIENTS AND MEASUREMENTS: Thirty-one consecutive newborns with permanent primary congenital hypothyroidism diagnosed by a screening programme were recruited from the outpatient clinic of a district hospital and underwent psychometric evaluation with the Wechsler Intelligence Scales after a minimum follow-up of 4 years. RESULTS: Eight of the 31 patients (25.8%) presented impaired intellectual development (full-scale intellectual quotient < 85), and one of them presented mental deficiency (full-scale intellectual quotient </= 69). The following were associated with worse prognosis: initial serum T4 levels </= 32.18 nmol/l, treatment beginning after 30 days of age, fewer than seven clinic visits during the first year of life, living in rural areas, nonintellectual parental occupation and little parental schooling. In a multiple regression analysis, only maternal schooling (B = 0.401; beta coefficient = 13.053, P = 0.063), number of clinic visits during the first year of life (B = 0.382; beta coefficient = 4.145, P = 0.047) and initial serum T4 (B = 0.287; beta coefficient = 1.336, P = 0.089) remained significantly associated with full-scale intelligence quotient scores. CONCLUSION: Maternal schooling, number of visits during the first year of life and baseline T4 levels were the main predictors of cognitive outcome in this cohort of patients.
Brazil↗
Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in Type 2 diabetes.
AIMS: To investigate the association of features of the metabolic syndrome with the prevalence of chronic complications. METHODS: A cross-sectional study was conducted with 548 patients with Type 2 diabetes mellitus (DM). Metabolic syndrome was diagnosed in the presence of at least two of the following: hypertension, dyslipidaemia, obesity, and microalbuminuria. RESULTS: Patients with the metabolic syndrome (85%) had a higher prevalence of peripheral vascular disease (PVD) (35% vs. 18%), retinopathy (44% vs. 20%), distal sensory neuropathy (DSN) (44% vs. 24%), micro- and macroalbuminuria (38% vs. 28%) and coronary artery disease (CAD) (53% vs. 36%). The more metabolic syndrome features (none/one, two, three or four), the higher the proportion of diabetes complications: PVD 18%, 31%, 37% and 38%; stroke 1.0%, 4.5%, 5.9% and 11.3%; retinopathy 20%, 38%, 42% and 64%; DSN 24%, 32%, 49% and 57%; micro- and macroalbuminuria 28%, 36% and 41%; and CAD 36%, 44%, 52% and 60% (P < 0.05). CONCLUSIONS: The metabolic syndrome and the aggregation of its components were significantly associated with macro- and microvascular complications in Type 2 DM patients.
Albuminuria↗
Conditions associated with very low values of glycohaemoglobin measured by an HPLC method.
AIMS: To identify the causes of very low glycohaemoglobin (GHb) values in a sample of patients with diabetes in southern Brazil using high performance liquid chromatography. METHODS: Between August 1996 and December 2001 all samples from patients with diabetes at a university hospital with GHb values below the reference range (4.7-6.0% HbA(1c)) were submitted to cellulose acetate electrophoresis. Medical records were reviewed to identify conditions that might be associated with these low values. RESULTS: Among 29 657 samples analysed, 130 patients had GHb < 4.7%. Seventy three patients (56%) were heterozygous for HbS, HbC, or HbD (19 black, two mulatto, and 52 white patients). The other 57 patients (44%) without Hb variants had low haematocrit and haemoglobin values (42 patients) or other conditions such as pregnancy, lipaemia, malignancy, cirrhosis, acetylsalicylic acid use, and absence of diabetes (15 patients). CONCLUSIONS: The presence of an Hb variant may falsely lower GHb measurements. However, anaemia is also a source of negative interference. The haematological status should be considered for the correct interpretation of GHb results.
Adolescent↗
Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing's disease.
Transsphenoidal pituitary surgery is the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure, there is no agreement regarding the definition of successful treatment. We prospectively studied postoperative serum cortisol dynamics in 41 patients with CD (including a total of 45 surgeries). The mean postoperative follow-up period was 4.8 yr. Remission was defined as clinical and laboratory signs of adrenal insufficiency, glucocorticoid dependence, and serum cortisol suppression on overnight oral 1-mg dexamethasone suppression test. Serum cortisol was measured preoperatively and postoperatively at 6, 12, and 24 h (28 surgeries) and at 10-12 d (45 surgeries). No statistical difference was detected in mean preoperative and 6-h postoperative cortisol levels between surgically induced remission patients [22.1 +/- 7.73 microg/dl (610 +/- 213.3 nmol/liter) and 25.2 +/- 19 microg/dl (695.2 +/- 524.4 nmol/liter)] and surgical failure patients [23.6 +/- 6.95 micro g/dl (651.4 +/- 161.8 nmol/liter) and 37.5 +/- 18.1 microg/dl (1035 +/- 499.6 nmol/liter); P = 0.50 and P = 0.17]. At 12 and 24 h after surgery, the difference was significant (P = 0.009 and P < 0.0001). Mean cortisol levels were 12.44 +/- 13.3 microg/dl (343.3 +/- 367.1 nmol/liter) and 4.72 +/- 6.72 microg/dl (130.3 +/- 185.5 nmol/liter) in the remission group and 26.3 +/- 7.06 microg/dl (725.9 +/- 194.8 nmol/liter) and 23.5 +/- 6.86 microg/dl (648.6 +/- 189.3 nmol/liter) in the failure group (P = 0.009; P < 0.0001). At 10-12 d after the procedure, the difference was also significant (P < 0.0001): cortisol levels were 2.52 +/- 3.32 microg/dl (69.5 +/- 91.6 nmol/liter) in the remission group and 24.9 +/- 13.3 microg/dl (687.2 +/- 367.1 nmol/liter) in the failure group. In conclusion, in the immediate postoperative period of transsphenoidal surgery, remission of CD is not necessarily defined by undetectable serum cortisol. During the first 10-12 d after surgery, cortisol nadir correctly classified the remission [cortisol, 7.0 microg/dl (193.2 nmol/liter) or less] and the failure groups [cortisol, 8.0 microg/dl (220.8 nmol/liter) or more]. Glucocorticoid should be administered only after laboratory and/or clinical evidence of adrenal insufficiency.
Adenoma↗
Accuracy of ultrasonography to establish the diagnosis and aetiology of permanent primary congenital hypothyroidism.
OBJECTIVE: To compare ultrasonography and 99mTc thyroid scintigraphy for the aetiologic diagnosis of permanent congenital hypothyroidism (CH). STUDY DESIGN: Eighty-eight consecutive patients with CH were recruited at an endocrinology outpatient clinic and submitted to high-frequency ultrasonography and to 99mTc scintigraphy. RESULTS: Seventy-six patients were diagnosed with permanent CH and 12 with transitory CH. The agreement between ultrasound and scintigraphy was very high (kappa coefficient = 0.866; P < 0.001) for the entire group. In permanent CH patients, ultrasonography identified 67 cases of dysgenesis (absence of thyroid gland in the usual anatomical location in 66 and hemiagenesis in one), and this diagnosis was confirmed by scintigraphy (absence of functional thyroid tissue in 43 and ectopia in 24). In the other nine permanent CH patients, the thyroid was in the usual anatomical location on ultrasonography but scintigraphy did not identify functional tissue in one patient. In the 12 transitory CH patients, a normally shaped thyroid was detected by ultrasound in the usual location, whereas scintigraphy showed absence of functional tissue in two identical twins and scarce concentration of isotope in a third patient. CONCLUSION: Ultrasonography is an accurate method to establish the presence of dysgenesis and might be used as the first imaging tool in patients with CH, whereas scintigraphy should be used mainly to distinguish agenesis from ectopia. Further examination is required to differentiate permanent CH with a normally located and shaped gland from transitory hypothyroidism.
Congenital Hypothyroidism↗
Ultrasonographic determination of goiter prevalence in southern Brazilian schoolchildren.
The aim of the present study was to estimate the prevalence of goiter in schoolchildren in a formerly iodine-deficient region in southern Brazil by assessing the relationship between body surface area (m2 ) and thyroid volume (ml) measured by ultrasonography. A population-based sample of 1,094 randomly selected schoolchildren (6 to 14 years; 556 boys and 538 girls) underwent clinical evaluation. A total of 119 (10.9%) children were diagnosed with goiter upon clinical examination according to WHO criteria (grade Ia: 65, grade Ib: 24, grade II: 29, grade III: 1). Of these, 85 underwent ultrasonography. In order to ascertain the absence of goiter in the 975 schoolchildren with a negative result upon clinical examination, one of ten children was randomly selected for ultrasonography. Sixty-two children agreed to be submitted to the exam. Thus, 147 schoolchildren were evaluated by ultrasonography (7.5-MHz transducer). Goiter was considered to be present when the thyroid volume:body surface area index was >6.2 ml/m . The estimated prevalence of goiter if all schoolchildren had been submitted to thyroid volume measurement by ultrasound was 7.2%; it was higher in the lower socioeconomic class (8.2%) than in the upper (7.8%) and middle classes (6.5%). In conclusion, the prevalence of goiter in schoolchildren of this region was higher than in other iodine-sufficient areas, especially in lower socioeconomic classes. Goiter in this region may be associated with naturally occurring goitrogens that operate more intensively among less privileged individuals.
Adolescent↗
Prolactin and growth hormone secretion after thyrotrophin-releasing hormone infusion and dopaminergic (DA2) blockade in infertile patients with minimal/mild endometriosis.
BACKGROUND: The origin of infertility in patients with endometriosis without tubal occlusion has not yet been clearly defined. Several reports show an abnormal pituitary-ovarian axis in this group of patients. Moreover, prolactin (PRL) and growth hormone (GH) secretion is closely related to reproductive status. This study aimed to evaluate PRL and GH secretion after metoclopramide and thyrotrophin-releasing hormone (TRH) infusion in infertile patients with minimal/mild endometriosis. METHODS: A total of 64 women participated in the study: 33 fertile patients without endometriosis; 10 fertile patients with minimal/mild endometriosis; and 21 infertile patients with minimal/mild endometriosis. TRH or metoclopramide was administered randomly in two sequential menstrual cycles (cycle days 3-5). Serum PRL and GH secretion before and after dopaminergic type 2 (DA2) receptor blockade and TRH were compared. RESULTS: Higher serum PRL levels were observed in patients with endometriosis at baseline and after 15 and 30 min of TRH administration. Also, infertile patients with endometriosis had lower serum estradiol levels than fertile patients. Moreover, the dopaminergic blockade did not result in abnormal PRL or GH secretion. CONCLUSIONS: Decreased serum estradiol levels and altered PRL secretion after TRH administration in infertile patients with minimal/mild endometriosis are related to ovulatory dysfunction and infertility in this group of patients without tubal occlusion.
Case-Control Studies↗
Ultrasonography in management of nodular thyroid disease.
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Biopsy, Needle↗
Hyperprolactinemia and luteal insufficiency in infertile patients with mild and minimal endometriosis.
The objective of the present paper was to assess the presence of hormonal alterations in infertile women with stage I or II endometriosis (Group III, n = 20) compared to fertile women without endometriosis (Group I, n = 14) and to fertile women with endometriosis (Group II, n = 7). Serum levels of FSH, LH, estradiol, TSH, and PRL were measured between days 1 and 5 of the early follicular phase; in the luteal phase, three serum samples were collected for progesterone measurement, and endometrial biopsies were performed. Serum estradiol levels were lower (p = 0.035) in infertile patients with endometriosis than in fertile patients without endometriosis. Six infertile patients with endometriosis presented prolactin levels above 20 ng/ml. This was not observed in the other groups. Luteal insufficiency was more frequent in infertile patients with endometriosis (78.9%) than in fertile patients with (42.9%) or without endometriosis (0%). In a multiple logistic regression analysis, only the presence of endometriosis and infertility was significantly associated with luteal insufficiency. The serum levels of LH, FSH, and TSH were not significantly different among the groups. Luteal insufficiency and altered prolactin secretion were associated with endometriosis, and could be important mechanisms causing infertility in this group of patients.
Adult↗
Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women.
In this report, we will describe the results of a cross-sectional study to assess PRL and GH secretion during the early follicular phase in 22 fertile patients after metoclopramide administration in order to achieve a dopaminergic DA2 receptor blockade. Blood samples were collected at - 15, 0, 15, 30, 45 and 60 minutes. PRL, GH, estradiol, IGF-I, TSH, glucose, and insulin were measured in the samples taken at - 15 and 0 minutes. The existence of a correlation between GH and PRL secretion was investigated. All patients presented normal serum levels of estradiol, prolactin, insulin, fasting glucose and IGF-I. Serum GH levels were not changed after metoclopramide infusion (p = 0.302), but there was a significant alteration in serum PRL (p = 0.0001) with the highest levels after 30 (mean: 237.20 ng/ml +/- 95.86) and 45 (mean: 211.80 ng/ml +/- 83.24) minutes. Serum GH levels did not correlate with serum PRL levels after the dopaminergic DA2 blockade. We conclude that GH secretion was not modulated by a direct effect of type 2 dopamine receptor.
Adult↗
The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a prospective, randomized study.
The effect of antithyroid drugs on the efficacy of radioiodine (131I) treatment is still controversial. This study evaluated the effect of methimazole pretreatment on the efficacy of 131I therapy in Graves' hyperthyroidism. Sixty-one untreated patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/d; 29 patients). 131I was administered 4 d after drug discontinuation. The calculated 131I dose was 200 microCi/g thyroid tissue as estimated by ultrasound, corrected by 24-h radioiodine uptake. Serum TSH, T4, and free T4 were measured 4 d before 131I therapy, on the day of treatment, and then monthly for 1 yr. Considering cure as euthyroidism or hypothyroidism, based on free T4 measurement, approximately 80% of patients from both groups were cured 3 months after beginning 131I treatment. After 1 yr the groups were similar in terms of persistent hyperthyroidism (15.6% vs. 13.8%), euthyroidism (28.1% vs. 31.0%), or hypothyroidism (56.3% vs. 55.2%). Relapsed patients presented larger thyroid volume (P = 0.002), higher 24-h radioiodine uptake (P = 0.022), and T3 levels (P = 0.002). Multiple logistic regression analysis identified T3 values as an independent predictor of therapy failure. In conclusion, pretreatment with methimazole had no effect on either the time required for cure or the 1-yr success rate of 131I therapy.
Adult↗