Could the presence of adrenal incidentaloma negatively affect COVID 19 outcomes?

BACKGROUND AND OBJECTIVE: Adrenal incidentalomas (AIs) are lesions larger than 1 cm that are incidentally detected in the adrenal glands. Chest computed tomography (CCT) is widely used in the first evaluation of patients with suspected coronavirus disease (COVID-19) that resulted in many incidental findings in the thorax and upper abdomen. In this study, we aimed to investigate the frequency of AI and their effects on the course and outcome of COVID-19 regardless of functional status. MATERIAL AND METHODS: We included 2493 patients aged between 18 and 99 years and whose adrenal glands were clearly visible in CCT images. They were divided into two groups: those with AI (AI group) and without AI (Control group). RESULTS: AI was detected in 148 (5.93%) patients and 80 (54.1%) of them were male. There was no difference in sex distribution between the groups, but the median age of patients with AI was significantly higher than those without AI [54.5 (20-94 years) vs. 42 (18-99 years); p < 0.001)]. In addition, in the AI group, both hospitalizations due to COVID-19-related conditions (30.4 vs. 21.2%, p = 0.008) and the mortality rate experienced during this time was significantly higher (14.7 vs. 7%, p < 0.001) diseases. The AI group had a significantly higher comorbidity rate than the control group (61.5 vs. 41.9%, p < 0.001). The most common comorbid diseases were hypertension, cardiovascular diseases, diabetes mellitus, respiratory system diseases, and hyperlipidaemia. Advanced age and male gender in terms of mortality, advanced age and covid 19 positivity in terms of hospitalization were determined as significant risk factors. CONCLUSIONS: The presence of AI may increase the morbidity and mortality rates associated with COVID-19, regardless of their functional status. Therefore, patients subjected to CCT imaging for COVID-19-related lung diseases should also be evaluated for AI. Careful follow-up of patients with COVID-19 and AI is necessary to monitor the progression of COVID-19.

The relationship between carotid intima-media thickness and microvascular changes in retinal zones and optic disc in patients with type 1 diabetes mellitus.

PURPOSE: The aim of this study was to detect early retinal vascular changes with optical coherence tomography angiography (OCTA) in type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy and to evaluate the correlation of the results with carotid intima-media thickness (IMT). DESIGN: This is a case-control and cross-sectional study. METHODS: This study included 38 adult patients with T1DM, and 38 age and gender-matched healthy controls. Retinal and optic disc (OD) measurements were taken using OCTA. The carotid artery IMT of each patient was measured using Doppler ultrasonography. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density, foveal avascular zone (FAZ), non-flow area (NFA) and foveal density (FD) were analysed in the fovea centred 6 × 6 mm macular area. The superficial capillary plexus and DCP were also scanned centred on the peripapillary region. The correlations between OCTA measurements and carotid IMT, duration of DM and haemoglobin A1c levels in patients with T1DM were evaluated. RESULTS: The mean values for carotid IMT were significantly higher in diabetic patients than in controls (p < 0.001). The mean values for vessel density SCP, DCP and OD were significantly lower in the diabetic group (p < 0.05). There were correlations between the carotid IMT and duration of T1DM and the evaluated parameters of OCTA. CONCLUSION: Microvascular changes in the SCP and DCP in patients with T1DM without DR offer important data. OCTA can be used to detect early microvascular changes in patients with T1DM without DR. In addition, a relationship was found between SCP vascular dropout and carotid IMT.

COVID-19 pandemic: what about the gonads?

The novel SARS-CoV-2 has spread to virtually all countries of the world infecting millions of people, the medical burden of this disease obviously being enormous. The gonads of both sexes are among the organs that may be affected by COVID-19 and/or may affect the severity of the disease. The clinical spectrum of SARS-CoV-2 infection clearly differs between genders. The current evidence indicates that the underlying mechanism of such an interaction could be associated with genetic, hormonal, and immunological differences, as well as with gender differences in such habits as smoking and alcohol use. On the other hand, there are controversies as to how and to what extent the gonads could be affected by COVID-19, possibly impacting upon sex steroids, fertility, and other functions. This review underlines the possible mechanisms that could clarify these questions concerning COVID-19 and the gonads. In addition, reference is made to potential new treatment modalities presently under investigation, these supported by accumulating data published in the recent literature.

Food Addiction Correlates with Psychosocial Functioning More Than Metabolic Parameters in Patients with Obesity.

Aim: To investigate the association of food addiction (FA) with the psychosocial functioning and metabolic parameters in obese patients seeking weight-loss treatment. Methods: Two hundred twenty-four obese patients (male/female: 28/196) with a mean age of 44.5 ± 13.4 years and body mass index (BMI) of 41.6 ± 7.2 were included in the study. After receiving sociodemographic data and medical history, detailed physical examination, including anthropometric measurements, was performed by an experienced physician. Blood samples were taken after 8-12 hr of fasting. The presence of FA was evaluated by using Yale Food Addiction Scale (YFAS). Psychological evaluation was performed by using a self-reported Patient Health Questionnaire-9 (PHQ-9) and health-related quality of life using the 36-item short-form health survey (SF-36). Results: Seventy-two of 224 (32.1%) patients met the criteria for FA, according to YFAS. The mean age of patients with FA was younger compared with patients without FA (P < 0.001). There was no statistically significant difference between the patients with and without FA in terms of BMI, fat percentage, and waist circumference (P = 0.440, P = 0.644, and P = 0.144, respectively). The depression frequency was significantly higher (61.1%, P < 0.001), while the SF-36 score of mental health was lower (P = 0.027) in patients with FA than in the patients without FA. Age- and sex-adjusted mean fasting plasma glucose level was lower in patients with FA (P = 0.021), but serum insulin levels, HOMA-IR (homeostasis model assessment of insulin resistance), HbA1c (hemoglobin A1c), lipid parameters, and vascular adiposity index were comparable. Conclusions: We found that FA frequency was very high in obese patients seeking treatment for weight loss, and it correlates with psychosocial functioning more than metabolic parameters.

Health Literacy and Weight Loss After Bariatric Surgery.

BACKGROUND: There are many factors that affect weight loss after bariatric surgery. The present study evaluated the impact of health literacy on weight loss after bariatric surgery in morbidly obese patients. METHODS: The data of 118 patients who underwent laparoscopic sleeve gastrectomy for morbid obesity (body mass index-BMI ≥ 40 kg/m2) and completed a 1-year follow-up period were recorded and evaluated, prospectively. The Turkish version of the 47-item European Health Literacy Survey Questionnaire (HLS-EU-Q47) was used to evaluate the health literacy of these patients. Their demographic characteristics, preoperative and postoperative weight (at 6 and 12 months), BMI, the percentage of excess weight loss (% EWL), excess BMI loss (% EBL) and total weight loss (%TWL), comorbidities, socioeconomic characteristics (marital status, income level, educational status, and duration), and HLS-EU-Q47 results were recorded and compared. RESULTS: A significant inverse relationship was identified between preoperative BMI and scores for health promotion health literacy and general health literacy indexes (p = 0.024 and p = 0.032, respectively). A significant positive relationship was noted between % EWL and % EBL at 6 and 12 months, and health promotion health literacy index scores (6 months: p = 0.004, p = 0.006; 12 months: p < 0.001 and p < 0.001, respectively). A similar significant positive relationship was recorded between the % EWL and % EBL at 12 months and the health care health literacy index scores (p = 0.042 and p = 0.036, respectively). There was also a significant positive relationship between general health literacy index scores and % EWL and % EBL at 12 months (p = 0.022 and p = 0.021, respectively). % EWL at 12 months increased by 0.39, with a 1-point increase in health promotion and health literacy index scores. CONCLUSIONS: A high health literacy index score in morbidly obese patients is associated with successful weight loss after bariatric surgery.

Even Short-Term Telmisartan Treatment Ameliorated Insulin Resistance But Had No Influence on Serum Adiponectin and Tumor Necrosis Factor-Alpha Levels in Hypertensive Patients with Metabolic Syndrome.

BACKGROUND: We investigated the effect of short-term telmisartan usage in addition to lifestyle changes such as diet and exercise on insulin resistance, lipid metabolism, and serum adiponectin and tumor necrosis factor-alpha (TNF-α) levels in hypertensive patients with metabolic syndrome (MetS). METHODS: A total of 36 hypertensive patients with MetS were randomized to telmisartan and control groups in an open-labeled prospective study. RESULTS: There were significant decreases in anthropometric variables of patients according to baseline measurements in both groups at the end of the study. Serum insulin level and insulin resistance assessed by homeostasis model assessment-insulin resistance were decreased significantly in the telmisartan group (P = 0.040 and P = 0.034, respectively) compared with the controls, while there was no statistically significant change in the lipid profiles of the two groups. Serum adiponectin level was increased by 19.1% ± 41.7% in the telmisartan group, but intergroup analysis revealed no significant change. There was also no significant change in serum TNF-α level in either group. CONCLUSION: It has been observed that even short-term telmisartan treatment had favorable effects on insulin resistance and glucose metabolism compared with lifestyle changes alone. The fundamental effect of telmisartan treatment on insulin resistance renders it a good therapeutic option for hypertensive patients with MetS.

Exenatide treatment causes suppression of serum fasting ghrelin levels in patients with type 2 diabetes mellitus.

AIM: In the present study, we investigated the long-term effects of exenatide treatment on serum fasting ghrelin levels in patients with type 2 diabetes mellitus. METHODS: Type 2 diabetic patients, who were using metformin with and without the other antihyperglycemic drugs on a stable dose for at least 3 months, were enrolled in the study. BMI>35 kg/m2 and HbA1c>7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs, other than metformin, were stopped, and metformin treatment was continued at 2000 mg per day. Exenatide treatment was initiated at 5 µg per dose subcutaneously (sc) twice daily, and after one month, the dose of exenatide was increased to 10 µg twice daily. Changes in anthropometric variables, glycemic control, lipid parameters and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment. RESULTS: Thirty-eight patients (male/female = 7/31) entered the study. The mean age of patients was 50.5 ± 8.8 years with a mean diabetes duration of 8.5 ± 4.9 years. The mean BMI was 41.6 ± 6.3 kg/m2 and the mean HbA1c of patients was 8.9 ± 1.4%. The mean change in the weight of patients was -5.6 kg and the percentage change in weight was -5.2 ± 3.7% following 12 weeks of treatment. BMI, fasting plasma glucose and HbA1c levels of patients were decreased significantly (P < 0.001 and P < 0.001; respectively), while there was no change in lipid parameters. Serum fasting ghrelin levels were significantly suppressed following 12 weeks of exenatide treatment compared with baseline values (328.4 ± 166.8 vs 245.3 ± 164.8 pg/mL) (P = 0.024). CONCLUSION: These results suggest that the effects of exenatide on weight loss may be related with the suppression of serum fasting ghrelin levels, which is an orexigenic peptide.

Exenatide Treatment Causes Suppression of Serum Ghrelin Levels following Mixed Meal Test in Obese Diabetic Women.

AIM: To investigate the effect of exenatide treatment on serum ghrelin levels in obese female patients with type 2 diabetes mellitus. METHODS: Fourteen female patients with type 2 diabetes mellitus being treated with metformin and exenatide were enrolled. A mixed meal test was applied to the patients while continuing with their daily medications. Blood samples were taken before and at 60, 120, and 180 minutes following mixed meal test to measure serum total ghrelin, glucose, and insulin levels. The following week, exenatide treatment of the patients was paused for 24 hours and the same experimental procedures were repeated. RESULTS: Serum ghrelin levels were suppressed significantly at 180 minutes with exenatide treatment compared with baseline (294.4 ± 57.5 versus 234.5 ± 59.4 pg/mL) (p < 0.001). Serum ghrelin levels at 180 minutes were statistically different when percentage change in serum ghrelin levels after mixed meal tests with and without exenatide usage were compared (p = 0.001). Estimated total area under the curve values for serum ghrelin concentrations was also significantly lower with exenatide compared with omitted treatment (p = 0.035). CONCLUSION: These results suggest that the effect of exenatide on weight loss may be related with the suppression of serum ghrelin levels, which is an orexigenic peptide.

Serum Levels of sRAGE Are Associated with Body Measurements, but Not Glycemic Parameters in Patients with Prediabetes.

BACKGROUND: Our aim was to assess serum levels of the soluble receptor for advanced glycation end products (sRAGE) and to examine their association with anthropometric and metabolic parameters in patients with prediabetes and obese controls. METHODS: The two study groups were composed of 42 patients with prediabetes and diabetic neuropathy and 42 age-, gender-, body weight (BW)-, and body mass index (BMI)-matched obese adults as the control group. Prediabetes was diagnosed by the following criteria issued by the American Diabetes Association: impaired fasting glucose [fasting plasma glucose (FPG) level of 100-125 mg/dL], impaired glucose tolerance (2 hr plasma glucose level of 140-199 mg/dL after a 75 grams oral glucose challenge), or a glycated hemoglobin (HbA1C) level of 5.7%-6.4%. RESULTS: There were no differences between the groups in terms of age, gender distribution, BW, or BMI. Despite these similarities, patients with prediabetes had higher FPG, HbA1c, and 2-hr postchallenge glucose levels, higher systolic and diastolic blood pressure, and larger waist and hip circumferences compared with the obese controls. Lipid measurements, complete blood counts, kidney and liver function tests, high-sensitivity C-reactive protein, and sRAGE levels were similar between the two groups. We found significant negative correlations between sRAGE levels and BW, BMI, waist and hip circumferences, waist-to-hip ratios, and low-density lipoprotein (LDL) cholesterol levels. There were no significant correlations with other parameters, including demographic, metabolic, and blood pressure measurements. CONCLUSIONS: In contrast to glycemic parameters, serum levels of sRAGE were negatively correlated with body measurements indicative of obesity in the prediabetic state. In addition, the negative correlation with LDL cholesterol levels suggests that sRAGE has a more robust association with metabolic syndrome than with prediabetes.

Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM.

AIM: To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM). MATERIAL AND METHODS: A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n = 30) or insulin alone (n = 31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications. RESULTS: Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64, P = 0.006; leptin 25.8 ± 17.6 to 20.1 ± 12.55, P = 0.006; group 2: resistin 7.16 ± 2.30 to 5.57 ± 2.48, P = 0.031; leptin 16.72 ± 16.1 to 14.0 ± 13.4, P = 0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98, P = 0.015, and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90, P = 0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower. DISCUSSION: The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion.

Serum macroprolactin levels in pregnancy and association with thyroid autoimmunity.

BACGROUND: To assess the contribution of macroprolactin to high serum prolactin levels and their association with thyroid status and thyroid autoimmunity during pregnancy. METHODS: 138 pregnant women who suspected of having thyroid dysfunction were studied and divided into three groups according to the thyroid status; group 1; euthyroidism (n 40), group 2; hypothyroidism (n 54), and group 3; hyperthyroid (n 44). Polyethylene glycol (PEG) precipitation method was used for detection of macroprolactin. A percentage recovery of 40 % or less is considered as macroprolactinemia. If macroprolactin was negative, the percentage of monomeric prolactin recovery (monoPRL %) after PEG precipitation was used for comparison between the groups. RESULTS: Macroprolactinemia was found in two patients (1.4 %) one from hypothyroid and other from euthyroid group. Basal prolactin levels in these patients were 400 and 403 ng/mL respectively. Referring to all patients, there was no correlation between PRL, macroPRL or monoPRL % with thyroid hormone status and also with the serum levels of thyroid antibodies (p > 0.05). A positive correlation was observed between the serum levels of PRL with TSH (p = 0.014 and r = 0.219), while a negative correlation was found with FT4 (p = 0.011 and r = -0.227). CONCLUSIONS: Despite the fact that serum prolactin levels were found to be high during pregnancy, the contribution of macroprolactin was found to be insignificant in our study. Unlike other auto immune diseases, we could not find any relationship between thyroid autoimmunity and PRL, macroPRL or monoPRL %. These results confirmed that measured prolactin was quite homogeneous during pregnancy.

Evaluation of serum Spondin 2 levels in the different stages of Type 2 diabetic nephropathy.

AIM: We aimed to determine whether serum SPON2 is a useful biomarker in the detection of Diabetic Nephropathy (DN) and to compare serum SPON2 levels with 24-hour urinary albumin excretion rate (UAER) in patients with DN at different stages. METHODS: The cohort included 80 adult patients with T2D and 20 healthy controls. The patients with T2D were divided into four groups according to UAER and serum creatinine (sCr) levels. Group 1 consisted of patients with normoalbuminuria (n = 20), Group 2 with microalbuminuria (n = 20), Group 3 with macroalbuminuria (n = 20) and Group 4 with albuminuria and sCr > 1.5 mg/dL (n = 20). RESULTS: There were no significant differences between the groups in terms of demographic data, C-reactive protein, HbA1c, lipids, serum uric acid levels and leukocyte counts. SPON2 levels were observed to increase linearly with increasing severity of diabetic nephropathy levels. The SPON2 levels of Group 4 were significantly higher than Group 1 and the controls, and SPON2 levels of Group 3 were significantly higher than Group 1. Blood urea nitrogen, creatinine and UAER were significantly positively correlated with SPON2; serum total protein and calcium levels were negatively correlated with SPON2 in patients with DN. CONCLUSION: We observed a linear and significant increase in SPON2 levels of patients with T2D as the stage of DN increased, but serum SPON2 level was not as effective as microalbuminuria in reflecting nephropathy. Also, serum SPON2 level was not as good as urine and tissue levels of SPON2 in detection of renal damage in DN.

Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome.

CONTEXT: Gordon Holmes syndrome (GHS) is characterized by cerebellar ataxia/atrophy and normosmic hypogonadotropic hypogonadism (nHH). The underlying pathophysiology of this combined neurodegeneration and nHH remains unknown. OBJECTIVE: We aimed to provide insight into the disease mechanism in GHS. METHODS: We studied a cohort of 6 multiplex families with GHS through autozygosity mapping and whole-exome sequencing. RESULTS: We identified 6 patients from 3 independent families carrying loss-of-function mutations in PNPLA6, which encodes neuropathy target esterase (NTE), a lysophospholipase that maintains intracellular phospholipid homeostasis by converting lysophosphatidylcholine to glycerophosphocholine. Wild-type PNPLA6, but not PNPLA6 bearing these mutations, rescued a well-established Drosophila neurodegenerative phenotype caused by the absence of sws, the fly ortholog of mammalian PNPLA6. Inhibition of NTE activity in the LßT2 gonadotrope cell line diminished LH response to GnRH by reducing GnRH-stimulated LH exocytosis, without affecting GnRH receptor signaling or LHß synthesis. CONCLUSION: These results suggest that NTE-dependent alteration of phospholipid homeostasis in GHS causes both neurodegeneration and impaired LH release from pituitary gonadotropes, leading to nHH.

Comparison of efficacy and safety of once- versus twice-daily insulin detemir added on to oral antidiabetics in insulin-naive type 2 diabetes patients: 24-week, crossover, treat to target trial in a single center.

AIM: To compare once- versus twice-daily insulin detemir added on OADS therapy in insulin-naive type 2 diabetes patients in terms of efficacy and safety. METHODS: An open-label study performed at a single center, comprised a randomized, crossover 24 week with insulin-naive type 2 diabetes patients. Insulin detemir was initiated with mean 0.12 U/kg in all patients (Group I once-daily, Group II twice-daily) and titrated for 24 week. RESULTS: A total of 50 patients completed the study (Group I n:25, Group II n:25). With use of once- and twice-daily insulin, HbA1c values were decreased by 1.8% (±2.0) and 1.5% (±1.4) within the first 12 weeks (p<0.01), whereas increased by 0.21% (±0.7) and 0.14% (±0.8) in the second 12 weeks (p>0.05). The increases in the insulin doses were found as 0.22 U/kg and 0.35 U/kg with once- and twice-daily insulin use, respectively (p:0.04). Although minor hypoglycemic events were similar in both groups in the first 12 weeks, 2-fold increase was found in the patients shifting from once- to twice-daily dose. Within the first and second periods, the body weight of the patients was observed an increase of 0.4 and 1.6 kg with once-daily dose, whereas a decrease of 0.1 and 2.1 kg in the twice-daily dose, in the same period. CONCLUSION: Once-daily use of insulin detemir up to 0.4 U/kg was found to have similar efficacy and safety as twice-daily use. Twice dose use of insulin did not provide a prominent glycemic control advantage on 1.5-fold higher use of insulin.

Body fat distribution has no effect on serum visfatin levels in healthy female subjects.

Obesity is the presence of either abnormal absolute amount or relative proportion of body fat. Contrary to gluteal obesity, visceral obesity is associated with different metabolic alterations including insulin resistance (IR). A relatively new adipocytokine visfatin is shown to be expressed predominantly in visceral fat and exhibit insulin-mimicking effects in rodents. It is still unclear whether serum visfatin levels are associated with increased total or visceral fat mass in humans. The aim of our study was to investigate the relation between visfatin and obesity parameters namely body mass index (BMI) and waist circumference (WaC) and IR in healthy female subjects. Eighty one female subjects 20 years of age, having no diagnosis of glucose intolerance or diabetes, hypertension and dyslipidemia were chosen. The patients were divided into four groups according to their BMI and WaC values. Serum visfatin and HOMA-IR levels did not differ among groups. No correlation was detected between serum visfatin levels and obesity and metabolic parameters. In conclusion, we demonstrated that body fat distribution did not affect serum visfatin levels in healthy female subjects. Further studies are needed to clarify the exact factors influencing and determining serum visfatin levels and its clinical reflections.

Comparative effects of pioglitazone and rosiglitazone on plasma levels of soluble receptor for advanced glycation end products in type 2 diabetes mellitus patients.

Low levels of soluble receptor for advanced glycation end products (sRAGE) have been associated with the occurrence of vascular complications in patients with type 2 diabetes mellitus. Preliminary evidence has suggested that thiazolidinediones have the ability to modulate circulating levels of this molecule in the hyperglycemic milieu. The aim of this pilot study was to assess the differential effect of 2 different thiazolidinediones-pioglitazone and rosiglitazone-on plasma levels of sRAGE in type 2 diabetes mellitus patients. Sixty type 2 diabetes mellitus subjects were randomly assigned to receive pioglitazone (30 mg/d, n = 19), rosiglitazone (4 mg/d, n = 20), or placebo (medical nutrition therapy, n = 21) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (homeostasis model assessment), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and sRAGE were evaluated at baseline and after 12 weeks. At 12 weeks, the pioglitazone (P < .001) group had a significant increase from baseline in sRAGE values that was not seen in the medical nutrition therapy and rosiglitazone groups. We conclude that, in type 2 diabetes mellitus patients, pioglitazone-but not rosiglitazone-significantly raised sRAGE, which may contribute to its antiatherogenic effects.

Comparison of composite whole body insulin sensitivity index derived from mixed meal test and oral glucose tolerance test in insulin resistant obese subjects.

Apart from fasting blood glucose (FBG) and insulin (FBI), oral glucose tolerance test (OGTT) is also used in calculating insulin sensitivity. During OGTT, insulin secretion may not reflect normal physiological insulin secretion. Based on this idea, hepatic and whole body insulin sensitivity rates were tested during OGTT and mixed meal test (MMT) in obese subjects. Thirty-one women with Quantitative Insulin Sensitivity Check Index (QUICKI) values below 0.350 and body mass index (BMI) >or=30 were included into the study. OGTT with 75-g glucose and MMT 300 kcal were applied to all cases. Data obtained from OGTT and MMT were used in the assessment of insulin sensitivity with Hemostasis of Model Assessment-Insulin Resistance (HOMA-IR) and Matsuda's Composite Whole Body Insulin Sensitivity Index (Matsuda's ISI). Mean BMI, FBG, and FBI were 36.8 +/- 3.9 kg/m(2), 100.5 +/- 0.10 mg/dl, 16.2 +/- 5.3 microg/ml, respectively. QUICKI was 0.31 +/- 0.01 and HOMA-IR was 3.71 +/- 0.88. Matsuda's ISI derived from OGTT was 6.96 +/- 3.35 and from MMT was 11.32 +/- 6.61. In analysis, it was demonstrated that there was a correlation between HOMA-IR, QUICKI, and Matsuda's ISIs derived from OGTT and MMT. Comparing the time periods separately, it was detected that despite similar increment in insulin levels, glucose levels were higher in OGTT than MMT at 15 and 30 min. Consequently, Matsuda's ISI was demonstrated to be effectively used with the data of MMT, as used with OGTT. Moreover, MMT was shown to be in parallel to physiologic insulin secretion and reflect pancreatic functions better compared to OGTT.

TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction.

The timely secretion of gonadal sex steroids is essential for the initiation of puberty, the postpubertal maintenance of secondary sexual characteristics and the normal perinatal development of male external genitalia. Normal gonadal steroid production requires the actions of the pituitary-derived gonadotropins, luteinizing hormone and follicle-stimulating hormone. We report four human pedigrees with severe congenital gonadotropin deficiency and pubertal failure in which all affected individuals are homozygous for loss-of-function mutations in TAC3 (encoding Neurokinin B) or its receptor TACR3 (encoding NK3R). Neurokinin B, a member of the substance P-related tachykinin family, is known to be highly expressed in hypothalamic neurons that also express kisspeptin, a recently identified regulator of gonadotropin-releasing hormone secretion. These findings implicate Neurokinin B as a critical central regulator of human gonadal function and suggest new approaches to the pharmacological control of human reproduction and sex hormone-related diseases.