Relationship between insulin sensitivity and degree of obesity in mild hypertension.

Eighteen patients with mild hypertension (diastolic blood pressure > or = 90 and < 104 mm Hg) and 15 normotensive control subjects were studied. Insulin tolerance tests (ITT) and fasting plasma insulin (FPI) level measurements were performed to evaluate insulin sensitivity. Insulin sensitivity, as measured with the ITT, showed a strong correlation with body mass index (BMI) in the hypertensive and control groups (r = -0.68, p < 0.01 and r = -0.61, p < 0.01, respectively). The fasting insulin levels also correlated significantly with BMI in both groups (r = 0.55, p < 0.05 in the hypertensive and r = 0.76, p < 0.01 in the control group). Insulin sensitivity in the hypertensive subjects whose BMI was < or = 27.0 kg/m2 (nonobese), as measured with the ITT and FPI, was not different from the nonobese normal controls (K(itt), 5.36 +/- 1.74% min-1 versus 5.61 +/- 1.66% min-1, respectively, p > 0.2; FPI, 5.8 +/- 3.4 microU/ml versus 7.1 +/- 2.5 microU/ml, respectively, p > 0.2). Also, insulin sensitivity, as measured with the ITT, was not statistically significantly different between hypertensive and normotensive obese subjects (K(itt), 2.82 +/- 1.55% versus 3.90 +/- 0.67% min-1, respectively, p > 0.1). When fasting plasma insulin levels were compared, a higher level was observed in the obese normotensive subjects than in the obese hypertensive group (FPI, 19.8 +/- 10.0 microU/ml and 11.5 +/- 4.9 microU/ml, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism

The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid.     

Is serum C-reactive protein concentration correlated with HbA1c and insulin resistance in Type 2 diabetic men with or without coronary heart disease?

BACKGROUND AND AIMS: C-reactive protein (CRP) is an inflammatory marker that predicts coronary heart disease (CHD) risk. Diabetes mellitus (DM) counts as a CHD risk equivalent. We aimed to compare serum high sensitivity CRP (hs-CRP) levels in Type 2 diabetic (T2DM) men without CHD, non-diabetic CHD patients and T2DM patients with CHD. SUBJECTS AND METHODS: Four groups were formed; Group 1 [DM(+), CHD(-), no.=25], Group 2 [DM(-), CHD(+) no.=25], Group 3 [DM(+), CHD(+), no.=25], and Group 4 (controls, no.=30). Serum hs-CRP, insulin, glucose, total, HDL-, LDL- and VLDL-cholesterol, triglyceride levels and homeostasis model assessment for insulin resistance (HOMA-IR) index were determined. RESULTS: Mean hs-CRP level of Group 1 (0.6+/-0.29) was not different statistically from Group 2 (1.44+/-0.97). Mean hs-CRP levels were higher in men with CHD, whether they were diabetic (Group 3; 3.83+/-2.01 mg/dl) or non-diabetic (Group 4), than in control subjects (0.16+/-0.15; p=0.0001 and p<0.004, respectively). Mean hs-CRP level of Group 3 was also higher than Group 2 (p=0.0001). There was a positive correlation between serum hs-CRP and glycated hemoglobin (HbA1c; r=0.277, p<0.01), fasting insulin (r=0.336, p<0.02) and HOMA-IR (r=0.348, p<0.02) in T2DM men with or without CHD. CONCLUSIONS: T2DM men without CHD had similar CRP levels with non-diabetic CHD patients, whereas CRP levels of T2DM men with CHD were higher than non-diabetic men with CHD. Because of a positive correlation between serum hs-CRP and HbA1c, fasting insulin and HOMA-IR, inflammation, insulin resistance and hyperglycemia jointly contribute to the cardiovascular risk in T2DM men.     

Insulin resistance and secretion in polycystic ovarian disease

In order to verify the relationship between insulin resistance and hyperandrogenism in Polycystic ovary disease (PCOD), circulating levels of insulin in response to oral glucose tolerance test (OGTT) were assessed in 23 PCOD patients and 10 matched control subjects without obesity, acanthosis nigricans and impaired glucose tolerance. In PCOD patients serum total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), LH and LH/FSH ratio were significantly higher than in control subjects; whereas urinary 17-ketosteroids (17-KS) and glycemic response to OGTT were not different. PCOD patients were clearly hyperinsulinemic before and during OGTT compared to the control group: mean +/- SD basal insulin (Io) (23.4 +/- 10.3 vs 11.3 +/- 4.6 microU/ml, p less than 0.001) and the sums of insulin levels (sigma I) during OGTT (341.4 +/- 148.9 vs 162.2 +/- 56 microU/ml, p less than 0.001). In the two groups serum T, but not DHEA-S, LH, urinary 17-KS and the degree of obesity, was strongly associated with Io (r = 0.458, p less than 0.01) and sigma I (r = 0.419, p less than 0.02), as well as with insulin resistance as assessed by basal (r = 0.425, p less than 0.02) and postglucose challenge (r = 0.384, p less than 0.05) insulin to glucose ratio. These results confirm that the hyperinsulinism and insulin resistance in PCOD is not related to obesity and suggest that the hyperandrogenism may be partially responsible of the observed imbalance in glucose-insulin homeostasis.     

Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men

OBJECTIVE: To investigate whether the changes in IGF-I concentrations after weight reduction in Japanese overweight men are associated with changes in visceral and subcutaneous fat. DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: One-hundred and twelve Japanese overweight men aged 30-59 y (body mass index (BMI) 28.4+/-2.5 kg/m(2)) and 33 normal-weight men aged 30-39 y (BMI 22.1+/-1.5 kg/m(2)) at baseline. From the participants, 56 randomly selected overweight men (BMI 28.8+/-2.8) were further enrolled into a 1 y exercise program. MEASUREMENTS: Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, metabolic parameters and hormones including insulin, leptin and IGF-I at baseline and after 1 y. RESULTS: In 112 overweight subjects at baseline, insulin (10.5+/-5.0 microU/ml) and leptin (6.4+/-3.7 ng/ml) significantly correlated with both V (r=0.260, P=0.0073; r=0.410, P<0.0001) and S areas (r=0.377, P<0.0001; r=0.613, P<0.0001), respectively. IGF-I (156.8+/-48.7 microU/ml) significantly and negatively correlated with V area (r=-0.242, P=0.0125) and age (r=-0.192, P=0.0480). In normal-weight men aged 30-39 y (n=33) and age-matched subjects (n=30) selected from the 112 overweight men, the serum IGF-I further tightly correlated with V area (r=-0.467, P<0.0001). Visceral fat area and age were independently related to serum IGF-I levels by multiple regression analysis. By intervention with exercise education, 56 overweight subjects showed an increase in daily steps (6224+/-2781 to 7898+/-4141 steps/day) and reduction of BMI (28.8+/-2.8 to 27.7+/-2.9). deltaIGF-I significantly correlated with deltaV area (r=-0.432, P=0.0009) but not with DeltaS area or deltaBMI. CONCLUSION: The present study indicated a negative correlation between IGF-I levels and visceral fat at baseline as well as an association between the reduction in visceral fat and increase in IGF-I levels after an exercise intervention.     

24-hour thyroid-stimulating hormone secretory pattern in elderly men

A chronobiological study was carried out in 10 elderly male subjects (78-83 years) to evaluate the 24-hour thyroid-stimulating hormone (TSH) secretory pattern. 10 young adult males (26-35 years) made up the control group. Hourly blood samples were drawn from each subject for a 24-hour period. TSH levels in elderly subjects showed blunted circadian fluctuations compared to those seen in young adult subjects. Mean 24-hour TSH values in elderly (3.1 +/- 0.3 microU/ml) and young adult subjects (3.5 +/- 0.1 microU/ml) did not differ statistically, but nighttime TSH values observed in elderly subjects (3.2 +/- 0.3 microU/ml) were lower (p less than 0.05) than those recorded in young adults (4.1 +/- 0.1 microU/ml).     

Blunted nocturnal TSH surge does not indicate central hypothyroidism in patients after pituitary surgery.

The thyrotropin-releasing hormone stimulation test (TRH test) is commonly used as part of the endocrine evaluation after pituitary surgery. However, some patients with a normal thyrotropin (TSH) response to TRH after pituitary surgery develop central hypothyroidism during follow-up. On the other hand, hypothyroidism does not necessarily ensue in patients with a blunted TSH response. As TSH is secreted in a pulsatile fashion with maximum secretion in the early morning, we investigated whether measurement of the nocturnal TSH surge is useful for predicting development of thyrotropic function after pituitary surgery. Serum TSH concentrations were measured at hourly intervals from 16.00 h to 06.00 h in 13 healthy volunteers and in 10 patients within 2 weeks after pituitary surgery. A standard TRH test using i.v. injection of 200 microg synthetic TRH was performed the next morning. Three and six months later thyroid function was reassessed in all patients by measuring thyroid hormones and TSH. Healthy volunteers showed a clear nocturnal TSH surge from a nadir of 0.55 +/- 0.27 microIU/ml at 18.00 h to a peak concentration of 1.82 +/- 0.97 microU/ml at 06.00 h (p = 0.0015). DeltaTSH during TRH test was 6.31 +/- 2.27 microIU/ml. In contrast, following pituitary surgery, patients invariably showed a blunted nocturnal increase in TSH concentration, which was 0.27 +/- 0.20 microIU/ml at 18.00 h and 0.33 +/- 0.26 microIU/ml at 06.00 h (p = 0.044). DeltaTSH during TRH test was 1.99 +/- 2.51 microIU/ml and was subnormal in 8 out of 10 patients. Levothyroxine supplementation was initiated in two of these patients, because free T4 levels were also subnormal and clinical hypothyroidism was present. In the remaining patients with subnormal TRH response, no case of central hypothyroidism was identified at the follow-up visits after 3 and 6 months. We conclude from these data that both nocturnal TSH surge and TRH test are subnormal after pituitary surgery and do not indicate that central hypothyroidism will develop.     

Reduced effect of experimental peripheral hyperinsulinemia to elevate cerebrospinal fluid insulin concentrations of obese Zucker rats

To test the effect of chronic hyperinsulinemia on cerebrospinal fluid (CSF) insulin concentrations in the obese (fafa) Zucker rat, obese and heterozygote lean (Fafa) rats were infused peripherally with insulin or vehicle for 6 days. Both basal levels and the increase of plasma immunoreactive insulin (IRI) were greater in fafa (increase = 713 microU/ml) than in Fafa (increase = 392 microU/ml) rats, P less than 0.0001. Vehicle-infused fafa rats had higher CSF IRI levels than did vehicle-infused Fafa rats (4.3 +/- 1.2 microU/ml vs. 1.5 +/- 0.4 microU/ml, P less than 0.01). CSF IRI was elevated in both insulin-infused groups (P less than 0.001). After insulin infusion Fafa rats had higher CSF IRI levels than did fafa rats (Fafa: 10.0 +/- 1.8 microU/ml vs. fafa: 7.1 +/- 0.1 microU/ml). In contrast to the effect of insulin infusion on plasma IRI, the increase of CSF IRI was greater in Fafa rats (8.5 microU/ml) than in fafa rats (4.0 microU/ml, P less than 0.001). Uptake of insulin from the periphery to the CSF therefore appears to be reduced in obese fafa Zucker rats compared to lean Fafa controls.     

Autoimmune thyroid disease in the puerperium. Predictive value of thyroid enlargement and related hormonal changes occurring during pregnancy

The incidence of goiter detected during pregnancy and its significance as an indicator of autoimmune thyroid disease after delivery was investigated in a sample of 707 pregnant women (81% in their 2nd trimester of gestation). Goiter was detected in 106 subjects (15%). Blood T4, T3, TSH, free T4 index (FT4I), antimicrosomal antibodies (AMA) and urinary iodine excretion were measured in these women and in a control group of gravidas without goiter. These measurements were repeated at 1 and 3 months after delivery. Compared with controls during pregnancy, subjects with goiter had lower FT4I values (11.0 +/- 2.8 vs 9.0 +/- 1.8; p less than 0.01) and higher TSH values (2.9 +/- 0.6 microU/ml vs 4.2 +/- 2.1 microU/ml; p less than 0.01). In contrast, T4, T3, AMA and urinary iodine excretion values were similar in both groups. In subjects with goiter FT4I values increased over pregnancy levels at 1 month (11.2 +/- 2.0; p less than 0.05) and 3 months (14.0 +/- 3.0; p less than 0.05) after delivery; in 29% a biochemical hyperthyroidism (FT4I greater than 13.5) was detected. During the same period TSH values decreased significantly (1 month: 1.9 +/- 0.7 microU/ml; p less than 0.05; 3 months: 2.7 +/- 3.0 microU/ml; p less than 0.05). Frequency of positive AMA increased from 8.6% during pregnancy up to 32.1% in the post-delivery period (p less than 0.01). In the control group no variation in the FT4I, TSH or AMA were observed after delivery. These results indicate that goiter during pregnancy is common in Chilean gravidas and that it has predictive value for the appearance of autoimmune thyroid disease after delivery.     

IODIDE ADMINISTRATION ENHANCES THYROTROPHIN RESPONSIVENESS TO THYROTROPHIN-RELEASING HORMONE DURING FASTING: EVIDENCE FOR NORMAL PITUITARY FEEDBACK REGULATION

Short-term fasting in humans is associated with diminished delta TSH to TRH. The purposes of the present study were to reassess basal TSH levels and TRH responsiveness during fasting utilizing a sensitive radioimmunoassay (RIA: sensitivity 0.3 microU/ml; normal range 0.66-2.98 microU/ml) and to determine if normal feedback regulation is maintained during the fasting state. Eight control subjects (C) and six iodide-treated (I) subjects (262 mg/d) were studied in the fed state and on day 10 of fasting. T3, T4, and TSH were measured by RIA, and free T4 and free T3 by equilibrium dialysis. Basal serum TSH levels in the control group were 2.0 +/- 0.3 microU/ml (mean +/- SEM) in the fed state and increased to 14.7 +/- 3.5 microU/ml 20 min after TRH administration. The fasting basal TSH level of 1.6 +/- 0.3 microU/ml was significantly decreased (P less than 0.01) compared to control, as was the level of 8.8 +/- 2.3 microU/ml (P less than 0.01) obtained 20 min after TRH. In the iodide-treated group the basal TSH level was 1.4 +/- 0.2 microU/ml during feeding which increased (P less than 0.025) to 2.9 +/- 0.7 microU/ml during fasting; the TSH value 20 min after TRH was 12.6 +/- 2.5 microU/ml while feeding and 17.3 +/- 2.9 microU/ml while fasting. Free and total T3 decreased during fasting in both groups. Total T4 was unchanged between the fed and fasted periods in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flow associated (endothelium dependent) vasodilation and TSH-levels in young normotensive and normoglycemic subjects.

BACKGROUND: Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Recent experimental data showed a crosstalk between endothelial NO-synthase activity and thyrotropin production. Therefore we studied whether basal TSH can predict flow associated vasodilation (FAD) in a cohort of healthy young subjects with normal TSH levels. PATIENTS AND METHODS: FAD was evaluated in 60 normotensive and normoglycemic subjects (mean age 34 years; range 18-50). The mean thyrotropin level was 1.43 +/- 0.11 microU/ml (range 0.18-3.52 microU/ml). RESULTS: Comparing subjects in the upper, middle and lower tertile of TSH (2.38 +/- 0.14 microU/ml, 1.23 +/- 0.04 microU/ml and 0.65 +/- 0.06 microU/ml respectively) there was no difference in terms of the classical cardiovascular risk factor profiles (24 h blood pressure, HDL- and LDL-cholesterol, triglycerides, oral glucose load and body fat content). Regarding the vascular parameters, we could neither find an independent association with FAD (7.0 +/- 1.1%, 6.4 +/- 1.0% and 5.8 +/- 1.1% respectively) nor with endothelial independent vasodilation (after application of glycerol trinitrate GTN, 17.3 +/- 1.9%, 18.4 +/- 1.7% bzw. 17.5 +/- 1.6% respectively) between the groups. Furthermore, we could not find a significant association between free thyroid hormones (fT3/fT4) and FAD or GTN-induced vasodilation. CONCLUSION: TSH has no predictive value towards endothelial dysfunction in subjects with thyrotropin levels within the normal range.     

Insulin action and insulin secretion in newly diagnosed type 2 diabetic patients

To clarify the insulin action and insulin secretion in newly diagnosed type 2 diabetic subjects, we investigated insulin and C-peptide response to an oral glucose tolerance test (OGTT) in 15 newly diagnosed type 2 diabetic patients and 17 healthy subjects. For insulin action, we found fasting hyperinsulinemia (8.4 +/- 0.8 vs. 6.0 +/- 0.5 microIU/ml, p = 0.014), higher insulin resistance by homeostasis model assessment (HOMA) (4.33 +/- 0.2 vs. 1.34 +/- 0.1 microIU/ml.mmol/l, p < 0.001), and lower insulin sensitivity index (ISI) (51.0 +/- 0.7 vs. 104.0 +/- 0.8, p < 0.001) in newly diagnosed diabetic patients compared to normal subjects. For insulin secretion, the increments of AUCI (area under curve of insulin) and AUCC-P (area under curve of C-peptide) (increment of AUCI: 26.1 +/- 1.4 vs. 82.8 +/- 4.5 microIU/ml.hour, p < 0.001; increment of AUCC-P: 3.9 +/- 0.2 vs. 11.4 +/- 0.6 ng/ml.hour, p < 0.001), insulin secretion by HOMA model (20.7 +/- 1.2 vs. 79.1 +/- 3.8 IU/mol, p < 0.001), and ratio of 30 min increment of fasting insulin to glucose during OGTT (1.14 +/- 0.1 vs. 13.1 +/- 0.5 IU/mol, p < 0.001) were significantly lower in the newly diagnosed diabetic patients than normal subjects. In addition, body mass index (BMI) in our type 2 diabetes is relatively lower (24 +/- 0.65 kg/m2) than those in western countries. These findings revealed poor insulin action and decreased insulin secretion in relatively less obese Taiwanese with newly diagnosed type 2 diabetes.     

Increased serum thyroglobulin concentrations and impaired thyrotropin response to thyrotropin-releasing hormone in euthyroid subjects with endemic goiter in Sicily: their relation to goiter size and nodularity

Serum thyroglobulin (Tg), T4, T3, FT4, FT3, TSH concentrations and TSH response to iv TRH (delta TSH) were measured in 56 consecutive patients with (multi) nodular goiter from a severely iodine-deficient endemic goiter area in Northeastern Sicily and in 11 non goitrous euthyroid individuals living in the same area. Serum Tg concentrations were sharply increased in goitrous subjects (453 +/- 476 ng/ml) and related to thyroid size and the presence of nodules (chi 2 = 43.5, p less than 0.0005). Serum TSH levels measured in goitrous patients (2.1 +/- 0.9 microU/ml) were significantly lower than those measured in nongoitrous iodine deficient subjects (3.1 +/- 0.9 microU/ml, p less than 0.001) and decreased with increasing goiter size and nodularity (chi 2 = 27.3, p less than 0.05). A similar pattern was shown by the analysis of the delta TSH (chi 2 = 43.1, p less than 0.0005). These results suggest that at least a part of the largest and multinodular goiters become autonomously functioning with duration and growing in size. In 13 goitrous patients with absent or impaired response to TRH, a significant direct relation was apparent between log-Tg and goiter size and nodularity (r = 0.64) with an inverse relationship between serum FT3 and delta TSH (r = 0.73). A computed program analysis based on the combination of different independent variables (x) including age, thyroid size and nodularity, serum TSH, log-Tg and FT3, indicated the existence of a significant negative relationship between these variables and the TSH response to TRH (r = 0.75, p = 0).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy

The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 +/- 56 pg/ml to 548 +/- 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 +/- 34 pg/ml to 206 +/- 15 pg/ml (P < 0.0001); ghrelin levels on octreotide ranged between 26% and 70% of baseline levels. Serum ghrelin levels were suppressed significantly during the oral glucose tolerance test in both groups. Pretherapy ghrelin levels correlated negatively with serum insulin levels (r = -0.494; P = 0.03) and insulin resistance as estimated by the homeostasis model assessment score (r = -0.573; P = 0.01). In patients without diabetes mellitus, serum insulin levels in the surgical group were 19.7 +/- 5.4 microU/ml before surgery and fell to 9.7 +/- 0.93 microU/ml after surgery (P = 0.05); levels in the octreotide group were 13.9 +/- 2.8 microU/ml before and fell to 11.2 +/- 2.8 microU/ml on octreotide (P = 0.03). Pretherapy ghrelin levels did not correlate with weight or body mass index, but after therapy in the surgery group ghrelin correlated negatively with weight (r = -0.823, P = 0.012) as has been demonstrated by others in healthy subjects. Ghrelin secretion is dysregulated in active acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with the postsurgery normalization of GH and IGF-I and improved insulin resistance. In contrast to surgical therapy, long-acting octreotide therapy persistently suppressed serum ghrelin levels. It remains to be determined whether altered circulating ghrelin concentrations could impact on body composition changes in acromegaly.     

Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in thyrotoxicosis: a minimal model analysis

In order to evaluate simultaneously in thyrotoxic subjects the relative contributions of insulin secretion, insulin-sensitivity (SI) and glucose-mediated (SG) glucose disposal to overall glucose tolerance, seven non-obese patients with thyrotoxicosis were studied by the minimal model analysis of the frequently sampled intravenous glucose tolerance test, before and greater than 1 month after being rendered euthyroid, and compared with eight healthy control subjects. Basal glucose, C-peptide and glucagon levels were similar in all groups but, in the toxic and euthyroid states, basal insulin levels were significantly elevated compared to the control group (11.2 +/- 2.0 and 7.9 +/- 1.1 vs 5.1 +/- 0.6 microU/ml, mean +/- SE, P less than 0.02). FFA levels were raised in the thyrotoxic subjects prior to treatment (0.95 +/- 0.11 vs 0.68 +/- 0.08 and 0.54 +/- 0.08 mmol/l, P less than 0.02). Glucose tolerance (Kg) was reduced in the thyrotoxic subjects compared to the euthyroid state (1.16 +/- 0.12 vs 1.44 +/- 0.13 per min, P less than 0.025) and control group (1.44 +/- 1.0 per min, 0.05 less than P less than 0.1). First phase (phi 1) and second phase (phi 2) insulin release were both significantly elevated in the thyrotoxic and euthyroid states compared to the control group (phi 1 7.10 +/- 1.88 and 5.29 +/- 1.03 vs 1.72 +/- 0.17 microU/mg/min X 10(-2), P less than 0.01; phi 2 18.64 +/- 3.14 and 16.74 +/- 4.48 vs 9.23 +/- 0.74 microU/mg/min X 10(-2) respectively, P less than 0.02). SG was similar in all groups but SI was significantly reduced in the thyrotoxic subjects compared to the control group (2.24 +/- 0.62 vs 5.92 +/- 1.50/min/microU/ml X 10(4), P less than 0.02) and rose post-treatment in the euthyroid subjects (4.23 +/- 1.75/min/microU/ml X 10(4)). In the thyrotoxic subjects before and after treatment, log SI correlated negatively with basal FFA levels (r = -0.57, P less than 0.05) and with phi 2 (r = -0.58, P less than 0.05). The fractional clearance rate of insulin was unaltered by the thyrotoxic state. It is concluded that in thyrotoxicosis the impairment of Kg is due to reduced insulin sensitivity in the presence of enhanced insulin secretion, but glucose-mediated glucose disposal is unaltered by the toxic state.     

Hypothyroidism has no impact on insulin sensitivity assessed with HOMA-IR in totally thyroidectomized patients

The influence of thyroid hormones on insulin and glucose metabolism is controversial. We examined the impact of hypothyroidism on insulin sensitivity in 22 hypothyroid patients (15 females and 7 males, mean age 51.0 +/- 12.36 yrs). All subjects had a history of total thyroidectomy and radioiodine ablation for differentiated thyroid cancer. Each subject ceased levothyroxine treatment six weeks prior to admission. The controls were 17 healthy individuals, 6 women and 11 men, mean age 55.12 +/- 14.17 years. TSH, free thyroxine, and the HOMA index of insulin sensitivity, as well as HOMA B (%) and HOMA S (%) were assessed. Insulin sensitivity was compared between the groups, and the correlation between FT4 and TSH and insulin sensitivity was calculated. RESULTS: The mean FT4 was 4.6 +/- 4.64 pmol/L in the examined group vs. 16.2 +/- 1.8 pmol/L in controls, p<005; TSH 72.11 +/- 36.73 pmol/L vs. 1.24 +/- 1.07 pmol/L, p<0.005; plasma glucose 4.68 +/- 0.47 mmol/L vs. 5.04 +/- 0.62mmol/L, p=0.0436; plasma insulin 8.07 +/- 9.39 microU/mL vs. 7.24 +/- 4.06 microU/mL, p=0.7877; HOMA index 1.79 +/- 2.53 vs. 1.69 +/- 1.09, p=0.5148; HOMA B (%) 102.46 +/- 41.59 vs. 85.95 +/- 26.87, p=0.1926, and HOMA S (%) 150.46 +/- 95.90 vs. 153.80 +/- 108.85, p= 0.6710, in subjects and controls, respectively. The levels of insulin sensitivity did not differ significantly between the two groups. FT4 and TSH did not influence the insulin sensitivity in either group, the correlation was insignificant, respectively p=0.5426 and p=0.8175 in the examined group, and p=0.172 and p=0.4509 in the controls. CONCLUSION: Hypothyroidism has no impact on insulin sensitivity in the examined group.     

Relationship between diabetes mellitus-associated obstructive sleep apnea syndrome and hyperinsulinemia]

The purpose of this study was to examine the prevalence of sleep disordered breathing and background factors, especially hyperinsulinemia, in diabetic patients. The subjects were 70 patients randomly selected from 143 noninsulin-dependent diabetic patients hospitalized for educational purposes. Obstructive sleep apnea syndrome (OSAS) was diagnosed in 13 subjects, equivalent to a prevalence of 18.6%. The mean +/- S.D. immunoreactive insulin (IRI) values for 11 of the 13 OSAS patients (excluding insulin-treated patients) and for 49 non-OSAS patients were 10.7 +/- 6.8 microU/ml and 5.8 +/- 3.5 microU/ml, respectively. The value for the OSAS group was higher than that for the non-OSAS group (p = 0.04). However, a positive correlation between body mass index (BMI) and IRI was observed in both the OSAS (Y = 1.148 X - 20.006, r = 0.834, p = 0.001) and non-OSAS (Y = 0.466 X - 5.820, r = 0.524, p = 0.0001) groups. Multivariate analysis demonstrated that the presence of OSAS had a statistically significant influence on IRI (p = 0.001), but not on BMI (p = 0.391). These findings suggest that hyperinsulinemia may be exacerbated in diabetic patients with OSAS regardless of BMI.     

Effects of phenobarbital on hypothalamic-pituitary-thyroid axis in the rat

It has been reported that phenobarbital (PB) increases the peripheral clearance of T4 and T3 and decreases serum T4 and T3 concentrations in the rat, but serum TSH remains unchanged. To explore a possible direct effect of PB on TSH secretion at the hypothalamic-pituitary level, adult male rats were given PB 100 mg/kg or vehicle IP for 10 days. No difference in their thyroid weights was observed. In the PB-treated group serum T4 was decreased (PB, 3 +/- 0.2 micrograms/dl vs. control, 3.8 +/- 0.1 micrograms/dl, mean +/- SE, p less than .002), as was serum T3 (PB, 51 +/- 6 ng/dl vs. control, 70 +/- 5 ng/dl, p less than .05), but serum TSH remained unchanged. Pituitary TSH and hypothalamic TRH contents also were unchanged. Further studies were carried out similarly in the thyroidectomized hypothyroid rat to eliminate the effect of PB on serum T4 and T3 levels. PB or vehicle were started two days after thyroidectomy. By postoperative day 12, TSH levels in the PB-treated rats were lower than in the controls (PB, 697 +/- 62 microU/ml vs. control, 891 +/- 53 microU/ml, p less than .05). Pituitary TSH and hypothalamic TRH contents again were similar in both groups. When TRH (500 ng/kg body weight, IV) was given, the increment in serum TSH at 10 minutes was significantly lower in the PB group (PB, 53 +/- 26 microU/ml vs. control, 131 +/- 18 microU/ml, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous insulin secretion in newly diagnosed diabetic patients in Saudi Arabia

Diabetes mellitus is a major health problem in Saudi Arabia. The evaluation of endogenous insulin secretion at diagnosis has not yet been studied in this population. We have therefore studied fasting and post-glucagon stimulation levels of glucose, insulin and C-peptide in 216 newly diagnosed untreated diabetic patients. The mean +/- SD fasting insulin and C-peptide levels were 14.0 +/- 1.8 microU/ml and 1.8 +/- 0.4 ng/ml, while post-glucagon stimulation levels were 21.1 +/- 3 microU/ml and 2.4 +/- 0.4 ng/ml. There were significant post-stimulatory increment levels for insulin, from 4.9 to 13.7 microU/ml, and C-peptide from 0.2 to 1.3 ng/ml (P less than 0.001). Such increments did not affect specified age distribution. We found a significant correlation between the fasting levels and post-stimulation levels of C-peptide and insulin. Obesity correlated with higher basal and post-stimulation levels of both hormones (r = 0.67, P less than 0.001). The mean +/- SD fasting insulin and C-peptide levels were 18.5 +/- 9.1 microU/ml and 2.4 +/- 0.8 ng/ml for obese patients and 11.5 +/- 5.1 microU/ml and 1.9 +/- 1.1 ng/ml for non-obese patients. The type of diabetes among the Saudi adult diabetic patients studied is characterized by high basal C-peptide and insulin levels which increase significantly with stimulation, suggesting diminished but present endogenous B-cell function.