John G. Yovos

Serum Ghrelin, Leptin and Adiponectin Levels before and after Weight Loss: Comparison of Three Methods of Treatment – A Prospective Study

Background: Ghrelin is a peptide hormone with orexigenic properties, primarily produced by the stomach. Leptin and adiponectin are the two adiposity products that participate in body weight control. Leptin always decreases and adiponectin increases after weight loss. Different changes in fasting ghrelin levels have been reported following bariatric surgery. In this study, we compare the changes in fasting ghrelin, leptin and adiponectin levels in 3 groups of patients who achieved weight loss by either diet, MacLean vertical banded gastroplasty (VBG) or biliopancreatic diversion with duodenal switch (BPD-DS). Methods: Serum fasting ghrelin, leptin and adiponectin concentration was measured in 40 obese patients who achieved weight loss by either diet (n=14), VBG (n=13) or BPD-DS (n=13), before and after weight loss. The follow-up period was 18 months for BPD-DS and VBG and 6 months for diet. Serum ghrelin level was measured by ELISA. Results: BMI was significantly decreased in all 3 groups: 9.2±2.4% (P<0.01) following diet, 38.47±7.26% (P<0.01) after VBG, and 42.88±9.09% after BPD-DS (P<0.01). Serum fasting ghrelin level increased after diet (110.45±117.84%, P=0.002) and VBG (65.48±92.93%, P=0.001),but decreased after BPD-DS (−21.63±28.63%, P=0.019). Leptin concentration decreased and adiponectin increased in all groups. Conclusions: Unlike after diet or gastric restrictive surgery, BPD-DS is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of this operation. Sleeve gastrectomy seems to be the main cause of this reduction.

Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome

OBJECTIVE To determine the effect of treatment with vitamin D(3) analogue in the parameters of glucose metabolism in obese women with polycystic ovary syndrome (PCOS). DESIGN Observational study. SETTING Obese women with PCOS in an academic research environment. PATIENT(S) Fifteen obese women (mean age 28 +/- 1.3 years, mean body mass index 32.55 +/- 0.43) with documented chronic anovulation and hyperandrogenism were recruited into the study. INTERVENTION(S) Alphacalcidol (1-alpha-hydroxyvitamin D(3)) was administered orally 1 microg/day for 3 months. All subjects underwent a frequently sampled IV glucose tolerance test after a 10- to 12-hour overnight fast during a spontaneous bleeding episode before and after treatment with alphacalcidol. MAIN OUTCOME MEASURE(S) Peripheral insulin resistance and insulin effectiveness were estimated with minimal model. RESULT(S) The first phase of insulin secretion was significantly increased after treatment with alphacalcidol. A favorable statistically significant change also was observed in the lipid profile. CONCLUSION(S) Treatment with the vitamin D(3) analogue (alphacalcidol) could be of value in the management of PCOS.

Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices in patients with hypertension and type II diabetes

The aim of this study was to evaluate the validity and reliability of homeostasis model assessment-insulin resistance (HOMA-IR) index, its reciprocal (1/HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and McAuleys index in hypertensive diabetic patients. In 78 patients with hypertension and type II diabetes glucose, insulin and triglyceride levels were determined after a 12-h fast to calculate these indices, and insulin sensitivity (IS) was measured with the hyperinsulinemic euglycemic clamp technique. Two weeks later, subjects had again their glucose, insulin and triglycerides measured. Simple and multiple linear regression analysis were applied to assess the validity of these indices compared to clamp IS and coefficients of variation between the two visits were estimated to assess their reproducibility. HOMA-IR index was strongly and inversely correlated with the basic IS clamp index, the M-value (r=−0.572, P<0.001), M-value normalized with subjects’ body weight or fat-free mass and every other clamp-derived index. 1/HOMA-IR and QUICKI indices were positively correlated with the M-value (r=0.342, P<0.05 and r=0.456, P<0.01, respectively) and the rest clamp indices. McAuleys index generally presented less strong correlations (r=0.317, P<0.05 with M-value). In multivariate analysis, HOMA-IR was the best fit of clamp-derived IS. Coefficients of variation between the two visits were 23.5% for HOMA-IR, 19.2% for 1/HOMA-IR, 7.8% for QUICKI and 15.1% for McAuleys index. In conclusion, HOMA-IR, 1/HOMA-IR and QUICKI are valid estimates of clamp-derived IS in patients with hypertension and type II diabetes, whereas the validity of McAuleys index needs further evaluation. QUICKI displayed better reproducibility than the other indices.

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase

Background Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. Objective To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. Methods In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. Results Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 ± 2.6 to 41.9 ± 3.2 μmol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 ± 0.39 versus 4.40 ± 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 ± 1.8 versus 129.9 ± 1.7 mmHg, P < 0.001 for systolic BP and 76.0 ± 1.6 versus 71.9 ± 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = −0.78, P < 0.01 and r = −0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 ± 0.41 versus 7.55 ± 0.31 mmol/l, P < 0.001), insulin (94.0 ± 0.41 versus 79.5 ± 5.6 pmol/l, P < 0.01) and HbA1c (8.15 ± 0.24 versus 7.24 ± 0.19%, P < 0.001). Conclusions Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.

Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium-hydrogen exchange in hypertensive patients with Type 2 diabetes

Aims/hypothesis  To investigate the effect of oral calcium (Ca2+) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca2+ ([Ca2+]i) and the transmembrane sodium–hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension.

Effect of various treatments on leptin, adiponectin, ghrelin and neuropeptide Y in patients with type 2 diabetes mellitus

Introduction: Several peptides are involved in the regulation of food intake and energy expenditure, among which are leptin, adiponectin, ghrelin and neuropeptide Y (NPY). These peptides may be implicated in the obesity seen in the majority of patients with type 2 diabetes mellitus (T2DM). Areas covered: The present review considers: i) the role of leptin, adiponectin, ghrelin and NPY in patients with T2DM, and, ii) the effect of insulin as well as oral hypoglycemic, antihypertensive, hypolipidemic, antiobesity and antiplatelet agents on these peptides in patients with T2DM. Expert opinion: Patients with T2DM have either lower or similar leptin levels, decreased adiponectin and ghrelin levels, and increased NPY circulating levels compared with nondiabetic controls. Treatment with insulin, oral hypoglycemic, antihypertensive, hypolipidemic, antiobesity and antiplatelet drugs may influence the levels of these peptides. It is not widely appreciated that several drugs commonly administered to patients with T2DM can influence adipokine levels. The clinical relevance of these effects needs to be evaluated.

In vitro application of Mn-ferrite nanoparticles as novel magnetic hyperthermia agents

Manganese ferrite nanoparticles were synthesized by a facile, low-cost, environmentally friendly and high yield methodology based on the aqueous co-precipitation of proper salts. Firstly, structural, morphological and magnetic characterization schemes were performed to determine crucial factors for optimizing their heating potential, such as size, polydispersity, saturation magnetization and coercivity. In an effort to simulate the in vivo environment of animal tissue phantoms and study the thermal heating effects resulting from Brownian motion and hysteresis losses, nanoparticles at various concentrations were embedded in aqueous media of varying agar concentration. During the in vitro application healthy cells (primary bone marrow-derived osteoblasts and 3T3-L1 fibroblast-like preadipocytes) and human osteosarcoma Saos-2 cells were incubated with manganese ferrite nanoparticles. The heating profile of the particles was studied at different concentrations and in correlation with their potential cytotoxic effect. Our results revealed concentration dependent cytotoxicity profile and uptake efficiency together with variable specific loss power values yet with fast thermal response, opening novel pathways in material selection as hyperthermia agents.

The Incretin Effect and Secretion in Obese and Lean Women with Polycystic Ovary Syndrome: A Pilot Study

BACKGROUND Insulin resistance is considered to play an important role in the pathogenesis of polycystic ovary syndrome (PCOS) and in the progression to type 2 diabetes. Recent reports concentrate on a possible relationship between incretin secretion and beta-cell function in PCOS. The aim of the present study is to investigate the incretin effect in obese and lean women with PCOS. METHODS Twenty women with PCOS and ten age-matched healthy women were recruited in the study. The oral glucose tolerance test (OGTT) and isoglycemic test were carried out on each participant after an overnight fast at 2-weeks interval. Plasma levels of insulin, glucose, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) were assayed. RESULTS Obese women with PCOS demonstrated lower GIP concentrations (area under the curve [AUC]) in response to OGTT compared to the control group. The incretin effect was found significantly augmented in the obese women with PCOS compared to controls. This finding remained robust in the subgroup analysis including only body mass index (BMI)-matched healthy women. CONCLUSIONS Increased insulinotropic effect could counteract the blunted GIP response to OGTT in obese women with PCOS. It is suggested that the pathology of PCOS may also include impaired activity of the enteroinsular axis.

Expression of microRNAs that regulate bone turnover in the serum of postmenopausal women with low bone mass and vertebral fractures

BACKGROUND Circulating microRNAs (miRs) are currently being investigated as novel biomarkers for osteoporosis and osteoporotic fractures. AIM The aim of this study was to investigate serum levels of specific microRNAs, known regulators of bone metabolism, in postmenopausal women with low bone mass and with or without vertebral fractures (VFs). METHODS For the analysis, 14 miRs were isolated from the serum of 35 postmenopausal women with low bone mass and with at least one moderate VF and 35 postmenopausal women with low bone mass without fractures. Thirty postmenopausal women with normal BMD values and no history of fractures served as controls. Main outcome parameters were changes in the expression of selected miRs in the serum of patient population and compared with controls. RESULTS From the 14 miRs that were selected, we identified 5 miRs, namely miR-21-5p, miR-23a, miR-29a-3p, miR-124-3p and miR-2861 that were significantly deregulated in the serum of patients with low bone mass compared with controls. Serum miR-124 and miR-2861 were significantly higher, whereas miR-21, miR-23 and miR-29 were lower in patients compared with controls. In a sub-group analysis of the patient population, the expression of miR-21-5p was significantly lower among osteoporotic/osteopenic women with VFs, showing 66% sensitivity and 77% specificity in distinguishing women with a vertebral fracture. CONCLUSION This study identifies a differential expression pattern of miR-21-5p in the serum of women with low BMD and VFs.

Genetic variation in the visfatin (PBEF1/NAMPT) gene and type 2 diabetes in the Greek population

Visfatin (NAMPT formerly known as PBEF1) is an adipokine that is strongly expressed in visceral fat and has caused much debate among researchers, regarding its involvement in glucose homeostasis and insulin resistance. It was initially isolated from bone marrow cells, and its involvement in inflammatory procedures such as sepsis and acute lung inflammation is now evident. Several studies have also reported an association of plasma visfatin levels with obesity. We undertook an evaluation of the involvement of the NAMPT gene in the development of type 2 diabetes (T2DM) in the Greek population. We studied 178 patients with T2DM and 177 controls that were matched for sex, age and body mass index. We genotyped three tagging SNPs selected from the HapMap II CEPH European population as reference for the Greek population. These three SNPs tag another 12 SNPs over the entire NAMPT gene with a mean r(2) of 0.92. No indications of association with disease status were found with any of the tested variants or the inferred haplotypes. Results were also negative when the quantitative traits of weight and BMI were tested. Although our study covers common variants across the NAMPT gene, the possible involvement of rare variants in T2DM etiology cannot be ruled out and will require the investigation of very large numbers of cases and controls.