Peripheral glucose metabolism in human hyperthyroidism.

The present study was designed to determine the effect of spontaneous hyperthyroidism on the forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Ten normal subjects and 11 hyperthyroid patients were studied after an overnight fast (12-14 h) and for 3 h after ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Increased forearm glucose uptake was observed in the hyperthyroid patients compared to that in the normal subjects (1286 +/- 212 vs. 677 +/- 88 mumol/100 mL forearm.3 h) with enhanced glucose oxidation (443 +/- 40 vs. 147 +/- 29 mumol/100 mL forearm.3 h). Nonoxidative glucose metabolism was also greater in hyperthyroid patients than in normal subjects (842 +/- 234 vs. 529 +/- 90 mumol/100 mL forearm.3 h). Basal serum FFA levels were significantly higher in hyperthyroid than in normal subjects (0.252 +/- 0.025 vs. 0.182 +/- 0.022 g/L), as were the basal lipid oxidation rates in the forearm muscles of the thyrotoxic individuals (0.290 +/- 0.066 vs. 0.088 +/- 0.016 mg/100 mL forearm.min). After glucose ingestion, serum FFA levels and lipid oxidation rates declined significantly to equivalent values in both groups of subjects, and the similar basal insulin concentrations increased to significantly higher levels in the hyperthyroid patients. In conclusion, spontaneous human hyperthyroidism increases glucose uptake by the forearm muscles in the postabsorptive state and during an oral glucose challenge, with augmented fluxes of glucose through the oxidative and nonoxidative pathways.

Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion.

BACKGROUND: To better understand the pathogenesis of type 2 diabetes mellitus, insulin secretion and insulin sensitivity (IS) were evaluated in white Brazilians with impaired glucose tolerance (IGT), using the oral glucose tolerance test (OGTT) and the hyperglycemic clamp technique. METHODS: Twenty-five IGT subjects were individually matched with normal glucose-tolerant (NGT) subjects for demographic characteristics. At first, they were submitted to the OGTT and plasma glucose and insulin were measured. Of the 25 pairs, 20 could participate in the hyperglycemic clamp procedures, at a second visit. All participants had their plasma glucose levels equally increased to 180 mg/dl; this was maintained for three hours by variable glucose infusion. During the procedure, plasma glucose and insulin were measured at established intervals. RESULTS: In the postabsorptive state, the IGT subjects presented higher levels of plasma glucose, blood HbA1, and serum triglycerides, but similar plasma insulin levels. After the oral glucose load, early and total insulin release, in relation to glucose levels, were respectively, 43 and 67% lower in the IGT individuals. The index of whole-body IS was increased in the IGT individuals (4.36 +/- 1.71 vs 3.61 +/- 1.28 mg(-1). micro U(-1).100.ml2; p<0.05). By the hyperglycemic clamp technique first- (82 +/- 26 vs 215 +/- 88 micro U/ml; p<0.001) and second- (36 +/- 19 vs 73 +/- 44 micro U/ml; p<0.05) phases of insulin secretion was decreased in the IGT individuals, especially the first one. However, the groups did not differ in relation to the IS: IGT=13.52 +/- 7.27 and NGT=9.96 +/- 6.70 mg.ml/kg. micro U.min(-1); p > 0.05. Functional relationship of IS (y) on first-phase insulin release (x) showed a smaller (p<0.05) regression coefficient for the IGT group. CONCLUSION: Brazilians with IGT well-matched with NGT ones were characterized by impaired first- and second-phase insulin secretion (mainly the former), while defects in IS were not evident.

Pancreatic beta-cell defects in women at risk of type 2 diabetes.

We evaluated insulin release and insulin sensitivity in women with basal and/or postprandial hyperglycemia but normal oral glucose tolerance test (OGTT) in previous pregnancy (GHG). These women were individually matched with females without previous hyperglycemia (NGT). Both groups consisted of normal glucose-tolerant women at the time of this study. They underwent OGTT (75 g; n=32 pairs) and hyperglycemic clamp experiments (10 mmoll(-1); n=27 pairs) with plasma glucose, insulin, and C-peptide measurements and calculation of insulinogenic index, first- and second-phase insulin release, and insulin sensitivity index (ISI). The GHG group showed higher glycosylated hemoglobin levels (6.2+/-0.6% versus 5.8+/-0.8%; P<0.05); lower insulinogenic index at 30 min (134.03+/-62.69 pmol mmol(-1) versus 181.59+/-70.26 pmol mmoll(-1); P<0.05) and diminished C-peptide response in relation to glucose (4.05+/-0.36 nmol mmol(-1) versus 4.23+/-0.36 nmol mmol(-1); P<0.05) at OGTT. Both groups did not show difference in insulin secretion and ISI by hyperglycemic clamp technique. We concluded that in up to 12 years from index pregnancy, women with previous GHG, presenting normal glucose tolerance and well-matched with their controls, showed beta-cell dysfunction without change in ISI. As women with previous GHG are at risk of type 2 diabetes, beta-cell dysfunction may be its primary defect.

Effect of oral glucose on peripheral muscle fuel metabolism in fasted men.

1. The metabolic adaptations of peripheral muscle during a 5-day "modified" fast (daily oral intake of 200 g of glucose) were studied in 12 normal males. The volunteers were studied initially after receiving a balanced 2,400-kcal diet for at least 3 days (S1) and then after 5 days of modified fast (S2). The forearm muscle exchange of energy substrate (glucose) and the carbohydrate and lipid oxidation rates in muscle were measured during the postabsorptive state (S1) and after an oral glucose challenge (S2). 2. Glucose intolerance was not observed in either situation. Arterial glucose levels increased from a basal value of 83 mg/100 ml to 171 mg/100 ml in S1 and to 187 mg/100 ml in S2 at 30 and 60 min, respectively, and returned to basal values at 180 min in both studies. Increased forearm glucose uptake was observed in S2 compared to S1 (121.7 +/- 17.1 vs 92.6 +/- 12.0 mg 100 ml forearm-1 3 h-1), with decreased glucose oxidation (23.8 +/- 3.7 vs 30.4 +/- 4.7 mg 100 ml forearm-1 3 h-1) and increased glucose storage (98.0 +/- 16.6 vs 62.2 +/- 10.8 mg 100 ml forearm-1 3 h-1) as muscle glycogen. 3. Basal serum free fatty acid (FFA) levels were significantly more elevated in S2 than S1 (1030 +/- 95 vs 657 +/- 59 mumol/l; P less than 0.05) but were markedly reduced by glucose ingestion in both studies (352 +/- 33 (S2) vs 364 +/- 30 (S1) mumol/l at 120 min). Basal FFA oxidation was similar in both studies (0.091 +/- 0.015 (S1) vs 0.105 +/- 0.019 (S2) mg 100 ml forearm-1 min-1) and decreased significantly 3 h after glucose ingestion only in S1 (0.030 +/- 0.010 (S1) vs 0.078 +/- 0.020 (S2) mg 100 ml forearm-1 min-1; P less than 0.05). 4. The insulin response to oral glucose was similar in both studies (11,060 +/- 899 (S1) vs 11,078 +/- 918 (S2) microU ml-1 3 h-1), but the peak concentration occurred later (60 min (S2) vs 30 min (S1] and basal levels were significantly lower in S2 compared to S1 (9.2 +/- 1.7 vs 11.1 +/- 1.5 microU/ml; P less than 0.05). 5. These data show that the metabolic adaptations of normal subjects to a 5-day "modified" fast (daily oral intake of 200 g glucose) were increased muscle uptake of glucose, with reduced glucose oxidation and increased glucose storage in the form of muscle glycogen.

Hormonal and metabolic study of a case of adiposis dolorosa (Dercum's disease).

A case of a 43-year-old nonobese woman with adiposis dolorosa (Dercum's disease) is reported. Muscle glucose uptake and oxidation before and after ingestion of 75 g of glucose were similar to control group values, although a greater insulin release (16,578 vs 6,242 +/- 1,136 microU/3 h) occurred simultaneously. In vitro studies of abdominal normal and painful subcutaneous adipose tissue of the patient revealed lower responsiveness to norepinephrine and lack of response to the antilipolytic effect of insulin in the painful adipose tissue (0.98 vs 1.43 microM FFA/10(6) cells at 5.0 microM of norepinephrine). The disease was not correlated with the HLA system and there were no alterations in hormonal secretion at the pituitary, adrenal, gonadal, and thyroid levels. These findings indicate the presence of peripheral insulin resistance in this patient with adiposis dolorosa.

Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients.

To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) microU/ml, b) second-phase insulin secretion, 64 (41-86) vs 53 (37-83) microU/ml, and c) ISI, 14.8 (9.0-20.8) vs 16.8 (9.0-27.0) mg kg-1 min-1/ microU ml-1. Hepatic insulin extraction in FH+ subjects was similar to that of FH- ones at basal conditions (median, 0.27 vs 0.27 ng/microU) and during glucose infusion (0.15 vs 0.15 ng/ micro U). Normal glucose-tolerant Brazilian FH+ individuals well-matched with FH- ones did not show defects of insulin secretion, insulin sensitivity, or hepatic insulin extraction as tested by hyperglycemic clamp procedures.

Zinc acutely and temporarily inhibits adrenal cortisol secretion in humans. A preliminary report.

Hypo- and hyperzincemia has been reported to cause alterations in the adrenal secretion. To determine the acute effect of zinc on cortisol levels, we studied 27 normal individuals of both sexes aged 20-27 y after a 12-h fast. The tests were initiated at 7:00 AM when an antecubital vein was punctured and a device for infusion was installed and maintained with physiological saline. Zinc was administered orally at 8:00 AM. Subjects were divided into an experimental group of 13 individuals who received doses of 25, 37.5, and 50 mg of zinc and a control group of 14 individual who received 20 mL of physiological saline. Serial blood samples were collected over a period of 240 min after basal samples (-30 and 0 min). We detected an acute inhibitory effect of zinc on cortisol secretion during 240 min of the study period in the experimental group.

[Arterial dysfunction as a possible mechanism of cardiac injury in type II diabetic patients. A Doppler-echocardiographic study]. / Disfunção arterial como possível mecanismo de agressão cardíaca em pacientes com diabetes mellitus tipo II. Estudo Doppler-ecocardiográfico.

PURPOSE: To evaluate the left ventricular structure and function and the arterial stiffness in type II diabetic patients. METHODS: Thirteen diabetic patients, men and women (age 55 +/- 8 years) were included in the study. None of the patients had any other clinical disorders. Doppler-echocardiography and non-invasive monitoring of arterial blood pressure were performed. All the results were compared to an age and sex matched control group (n = 12). RESULTS: There were no differences between the groups for diastolic blood pressure, dimensions of cardiac chambers and ventricular systolic and diastolic function indexes. Diabetic patients had increased left ventricular mass index (101 +/- 10 vs 80 +/- 14 g/m2; p < 0.001) and increased arterial stiffness (0.86 +/- 0.26 vs 0.69 +/- 0.19 mmHg/mL; p < 0.05), when compared to control group. CONCLUSION: Diabetes mellitus is associated to increased systemic arterial stiffness and this may contribute to the adverse effects of diabetes on left ventricular morphology.

Demographic and metabolic characteristics of individuals with progressive glucose tolerance.

We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT) were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT), insulin secretion (first and second phases) and insulin sensitivity indices (from hyperglycemic clamp assay) for both groups. In the normal glucose tolerant phase, progressors presented: 1) a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2) a reduced first-phase insulin secretion (2.0 +/- 0.3 vs 2.3 +/- 0.3 pmol/L; P < 0.02) with a similar insulin sensitivity index and a lower disposition index (3.9 +/- 0.2 vs 4.1 +/- 0.2 micromol.kg-1.min-1 ; P < 0.05) vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05) and reduced early insulin response to OGTT (progressors, 1st: 2.10 +/- 0.34 vs 2nd: 1.87 +/- 0.25 pmol/mmol; non-progressors, 1st: 2.15 +/- 0.28 vs 2nd: 2.03 +/- 0.39 pmol/mmol; P < 0.05). Theses data suggest that beta-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

Increased glucose synthesis in renal tubule fragments from hyperthyroid rats.

Rates of glucose synthesis from several substrates were examined in renal tubule fragments from hyperthyroid rats. A hyperthyroid state was induced by daily intraperitoneal injections of thyroxine (T4) (100 microg/100 g body weight) for 14 days. At the end of the experimental period, plasma triiodothyronine and T4 levels were six and eight times higher, respectively, than initial values. Hyperthyroid rats gained less weight and had lower blood glucose despite an increased food intake. In both control and hyperthyroid rats, rates of glucose production by renal tubule fragments were higher with glutamine and glycerol than with lactate, alanine, or glutamate. T4 treatment induced a significant increase in the de novo glucose synthesis from all substrates, except glutamine. The highest percent increase was obtained with alanine (64%), compared with 31-40% for glutamate, lactate, and glycerol. The T4 treatment induced increase in glucose synthesis by renal tubule fragments suggests that renal gluconeogenesis contributes to enhance glucose production in hyperthyroidism.

Demographic and metabolic characteristics of individuals with progressive glucose tolerance

We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT) were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT), insulin secretion (first and second phases) and insulin sensitivity indices (from hyperglycemic clamp assay) for both groups. In the normal glucose tolerant phase, progressors presented: 1) a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2) a reduced first-phase insulin secretion (2.0 ± 0.3 vs 2.3 ± 0.3 pmol/L; P < 0.02) with a similar insulin sensitivity index and a lower disposition index (3.9 ± 0.2 vs 4.1 ± 0.2 µmol·kg-1·min-1 ; P < 0.05) vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05) and reduced early insulin response to OGTT (progressors, 1st: 2.10 ± 0.34 vs 2nd: 1.87 ± 0.25 pmol/mmol; non-progressors, 1st: 2.15 ± 0.28 vs 2nd: 2.03 ± 0.39 pmol/mmol; P < 0.05). Theses data suggest that β-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

Effect of glucose ingestion on peripheral glucose metabolism in normal man.

This study was designed to determine the forearm exchange of energetic substrates (glucose and free fatty acids) and the carbohydrate and lipid oxidation rates of normal individuals, in the postabsorptive state and after an oral glucose challenge. Seventeen healthy male volunteers were studied after an overnight fast (12-14 h) and during 3 hours after ingestion of 75 g of glucose. The forearm glucose uptake rate reached the maximum at 60 minutes (0.935 +/- 0.098 mg/100 ml of forearm.min), while 114.9 +/- 9.4 and 90.1 +/- 8.4 mg/100 ml of forearm were the total and incremental peripheral uptake of glucose in 3 hours of study, respectively. After the ingestion of 75 g of glucose, an increase in the oxidation rate of this hexose was observed, corresponding to an increment in the basal oxidation of 21.0 +/- 2.6 mg/100 ml of forearm in 3 hours. The arterial and venous plasma levels of free fatty acids decreased significantly after the glucose meal, associated with a decrease in the lipid oxidation rate. In conclusion, the results of this study showed that, in normal subjects after ingestion of 75 g of glucose, 30.3 +/- 2.1 g (40.4% of the ingested load) of this substrate were processed by the skeletal muscle in the body as a whole and 8.1 +/- 0.6 g were oxidized in this tissue during 3 hours.

Sex-related differences in peripheral glucose metabolism in normal subjects.

The metabolic response of muscle tissue to glucose ingestion was studied in 10 normal men (M) and women (F) by using the forearm balance technique and indirect calorimetry simultaneously. During the 3 hours after a 75 g--oral glucose load, glucose uptake per unit muscle mass was significantly higher in women than in men, F = 187.3 +/- 26.9 vs M = 116.7 +/- 9.5 mg/100 g forearm muscle (P less than 0.05). A significant difference in muscle glucose fate was also observed since the amount of glucose utilized through a nonoxidative pathway was significantly higher in women, F = 84.5 +/- 2.6% (161.8 +/- 27.3 mg/100 g forearm muscle) vs M = 75.3 +/- 2.2% (87.2 +/- 8.6 mg/100 g forearm muscle) (P less than 0.05), whereas the amount of glucose oxidized in relation to glucose uptake was significantly higher in men, M = 24.7 +/- 2.2% (28.2 +/- 3.2 mg/100 g forearm muscle) vs F = 15.5 +/- 2.6% (27.8 +/- 5.4 mg/100 g forearm muscle) (P less than 0.05). No significant differences in insulin response to glucose ingestion were detected between groups. The women showed greater suppression of serum free fatty acids (FFA) levels in relation to basal levels than men. We conclude that: 1) after ingesting 75 g glucose, normal women showed greater glucose uptake per unit muscle mass than normal men, 2) for 3 hours after the ingestion of 75 g glucose, the predominant tendency toward utilizing glucose by a nonoxidative pathway is more marked in normal women than in normal men, and 3) the higher glucose uptake per unit muscle mass in the female group in the presence of an insulin response not significantly different from that of the male group suggests that muscle insulin sensitivity is greater in normal women.

Zinc: an inhibitor of prolactin (PRL) secretion in humans.

The response of plasma prolactin (PRL) to oral administration of increasing doses of zinc (25.0, 37.5 and 50.0 mg) was studied in 17 normal adult men and women. Blood samples were collected at 10 and 30-min intervals over a period of 120 min after two basal times (-30 and 0 min). PRL concentrations significantly fell below basal levels in all subjects in response to the increase in plasma zinc levels, as compared to the controls. These results suggest that acute hyperzincemia can inhibit basal PRL secretion in normal individuals.

Epidemiological survey of skin diseases in schoolchildren living in the Purus Valley (Acre State, Amazonia, Brazil).

A total of 9,955 schoolchildren aged 6-16 years have been examined in a tropical region. The prevalence of dermatosis varied from 21 to 87% in the municipalities surveyed. The most common dermatoses were pediculosis (prevalence 50%), nevi (16.8%), pityriasis versicolor (13.2%), pyoderma (12.2%), pityriasis alba (9.9%), dermatophytosis (6.2%), viral dermatosis (6.2%), scabies (3.0%) and acne vulgaris (2.7%). The prevalence of angular stomatitis, miliaria rubra, candidiasis, piedra nigra, keratosis pilaris, ephelides and geographic tongue is lower but still relatively high. Females had higher rates of pediculosis capitis and males higher prevalence of pityriasis alba. The prevalence of pityriasis versicolor, pigmented nevus and scabies was similar in males and females. Folliculitis, macular pigmented nevi and especially pityriasis versicolor tended to increase with age. Leprosy is hyperendemic in the surveyed area and its rate in the schoolchildren examined was 0.08%. Population movement (urbanization), socioeconomic situation, living conditions, promiscuity, and lack of hygiene may be the cause of such high prevalence and of association of two or more skin conditions. Climatic conditions might have enhanced the prevalence of certain dermatoses (pityriasis versicolor, dermatophytosis, piedra nigra, candidiasis, miliaria rubra).