Degree Of Insulin Sensitivity Research Articles

Abstract 3025: Association Of Systemic Insulin Sensitivity With Walking Distance In Peripheral Artery Disease

Background: Skeletal muscle in patients with peripheral artery disease (PAD) is subjected to chronic ischemia and is known to be insulin resistant. The association of insulin resistance with walking distance in unclear. Research Question: Does systemic insulin sensitivity (assessed by Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] and Adipose tissue insulin resistance index [Adipo-IR]) associate with 6-minute walk test distance (6MWT)? Aims: To understand the role insulin resistance plays in ambulatory impairment in PAD. Methods: Patients with PAD (defined as ABI <0.85) and age-matched controls (ABI 1.00-1.40) were recruited and underwent measurements of fasting glucose, free fatty acids (FFA), and insulin followed by 6-minute walk testing. HOMA-IR was calculated as (glucose [mg/dL] x insulin [uU/mL])/405 and Adipo-IR was calculated as FFA (mmol/L) x insulin (uU/mL). Comparisons between controls and those with PAD were done with Mann-Whitney U tests. Linear regression modeling was used to assess the association of insulin sensitivity with 6MWT. Results: Seventy subjects (median [IQR] age 67.5 [61.0, 73.0] years, 45 (64.3%) males) were recruited, including 20 controls and 50 with PAD. Insulin levels were significantly high in those with PAD (9.6 vs 12.1 uU/mL, p=0.05) while FFA (0.37 vs 0.34 mmol/L, p=0.04) levels were lower. Glucose levels were similar (77.9 vs 79.5 mg/dL, p=0.53). HOMA-IR was significantly higher in PAD (2.4 vs 2.0, p=0.03) while Adipo-IR was similar (3.9 vs 3.7, p=2.42). Insulin level, HOMA-IR, and Adipo-IR were significantly associated with 6MWT distance in univariate analysis, but no association was seen after adjusting for ABI, which strongly associated with walking distance. Conclusion: Patients with PAD exhibit systemic insulin resistance, although ABI was more strongly associated with 6MWT distance than the degree of insulin sensitivity.

Renal Cortical Glucose Uptake Is Decreased in Insulin Resistance and Correlates Inversely With Serum Free-fatty Acids.

Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a noninvasive manner. We have recently demonstrated that fluorodeoxyglucose F18 (18F FDG) positron emission tomography can be used to analyze renal glucose uptake (GU) rates, and that the renal cortex is an insulin-sensitive tissue. To confirm that renal GU is decreased in people with obesity and to test whether circulating metabolites are related to renal GU. Eighteen people with obesity and 18 nonobese controls were studied with [18F]FDG positron emission tomography during insulin clamp. Renal scans were obtained ∼60 minutes after [18F]FDG injection. Renal GU was measured using fractional uptake rate and after correcting for residual intratubular [18F]FDG. Circulating metabolites were measured using high-throughput proton nuclear magnetic resonance metabolomics. Cortical GU was higher in healthy nonobese controls compared with people with obesity (4.7 [3.4-5.6] vs 3.1 [2.2-4.3], P = .004, respectively), and it associated positively with the degree of insulin sensitivity (M value) (r = 0.42, P = .01). Moreover, cortical GU was inversely associated with circulating β-OH-butyrate (r = -0.58, P = .009), acetoacetate (r = -0.48, P = .008), citrate (r = -0.44, P = .01), and free fatty acids (r = -0.68, P < .0001), even when accounting for the M value. On the contrary, medullary GU was not associated with any clinical parameters. These data confirm differences in renal cortical GU between people with obesity and healthy nonobese controls. Moreover, the negative correlations between renal cortex GU and free fatty acids, ketone bodies, and citrate are suggestive of substrate competition in the renal cortex.

Circulating microRNA levels differ in the early stages of insulin resistance in prepubertal children with obesity

AimsThe increasing prevalence of childhood obesity escalates the risk for related complications. Circulating microRNAs (miRNAs) have been suggested as good predictive markers of insulin resistance in those with obesity. The aim was to identify a circulating miRNA profile that reflects insulin resistance in prepubertal children with obesity. Material and methodsPlasma miRNAs were measured in prepubertal children (n = 63, 5–9 years) using TaqMan Advanced miRNA Human Serum/Plasma plates and then were validated by RT-qPCR. Subjects were divided into normal weight (n = 20, NW) and overweight or obese (n = 43, OW/OB) groups according to their BMI z-scores. The OW/OB group was further subdivided into insulin sensitive or metabolically healthy obese (n = 26, MHO) and insulin resistant or metabolically unhealthy obese (n = 17, MUO) according to HOMA-IR. Key findingsWhile no differences were observed in the fasting plasma glucose levels, serum insulin levels were significantly elevated in the OW/OB compared to the NW group. Of 188 screened miRNAs, eleven were differentially expressed between the NW and OW/OB groups. Validation confirmed increased circulating levels of miR-146a-5p and miR-18a-5p in the OW/OB group, which correlated with BMI z-score. Interestingly, miR-146a-5p was also correlated with HOMA-IR index. While only miR-18a-5p was upregulated in the OW/OB children, independently of their degree of insulin sensitivity, miR-146-5p, miR-423-3p and miR-152-3p were associated with insulin resistance. SignificanceThe present study provides evidence of molecular alterations that occur early in life in prepubertal obesity. These alterations may potentially be crucial for targeted prevention or prompt precision therapeutic development and subsequent interventions.

Association of Dietary Acid Load with Insulin Sensitivity Index among Apparently Healthy Nigerians

The possible role of regular consumption of diets with high acid forming potential in decreasing cellular sensitivity to insulin and its associated complications has been investigated. However, findings across different study groups are conflicting. It is likely that the association is affected by genetic and environmental factors that differ among different populations. We investigated the impact of diet-induced acidosis on the degree of insulin sensitivity among apparently healthy adult Nigerians. Assessment of dietary intake was done using a semi-quantitative food frequency questionnaire and the Nigerian Food Composition Table. Acid forming potential of our local diets were estimated as Potential Renal Acid Load (PRAL) scores. Fasting plasma glucose and insulin were measured. Degree of insulin sensitivity was calculated as Quantitative Insulin Sensitivity Check Index (QUICKI). About 35 (16.2%) of the study subjects were observed to have insulin resistance. Across the study groups, there was a statistically significant trend with higher intake of dietary acid associated with decreased insulin sensitivity (p for trend &lt; 0.05). We conclude that among apparently healthy adult subjects in this study, regular consumption of diets with high acid forming potential might be linked with worsening of insulin sensitivity.

Increased basal insulin sensitivity in late pregnancy in women carrying a male fetus: a cohort study

BackgroundIt has been suggested that fetal sex may be able to modify maternal metabolism and physiology during pregnancy. Recently pregnant women carrying a male fetus were reported to be more insulin sensitive than those carrying females, although related evidence is inconsistent.MethodsIn this study we administered a 75 g oral glucose tolerance test at around week 28 of pregnancy in 813 pregnant women from a contemporary birth cohort (the Cambridge Baby Growth Study), derived surrogate indices of insulin secretion and sensitivity, and related them to the fetal sex.ResultsCarrying a male fetus was associated with lower fasting glucose (difference in mean concentrations ≈ 0.1 mmol/L; β′ = 0.063; p = 0.02) and insulin (≈ 1.1 pmol/L; β′ = 0.075; p = 0.01) concentrations but not with post-load glucose or insulin concentrations. Male fetal sex was also associated with lower HOMA IR (≈ 1.08 units; β′ = 0.071; p = 0.02) and higher QUICKI (≈ 1.06 units; β′ = 0.080; p = 0.007) values suggesting increased basal insulin sensitivity. There were no differences in indices of insulin secretion, except for the insulin disposition index which was higher in women carrying a male fetus (≈ 1.15 units; β′ = 0.090; p = 0.007). Birth weights were higher in male offspring.ConclusionsWomen carrying a male fetus were relatively more insulin sensitive in the fasting state and secreted more insulin relative to this degree of insulin sensitivity. These results are consistent with the idea that the fetal sex may be able to modify the maternal glucose-insulin axis.

Adipose Tissue and Skeletal Muscle Expression of Genes Associated with Thyroid Hormone Action in Obesity and Insulin Resistance

Background: Thyroid hormone (TH) regulates metabolic pathways which may interfere with insulin action. There is limited knowledge on adipose tissue (AT) and skeletal muscle (SM) expression of genes associated with TH action in relation to insulin sensitivity. The aim of this study was to analyze AT and SM expression of the genes associated with TH action in subjects with different degree of insulin sensitivity and the regulation of these genes by insulin and free fatty acids (FFA). Methods: The study group comprised 72 euthyroid male subjects: 36 normal weight subjects and 36 overweight/obese subjects. Two-hour hyperinsulinemic-euglycemic clamp and tissue biopsies were performed. In the subgroup of 20 subjects, 9 normal weight subjects and 11 overweight/obese subjects, clamp was prolonged to 6 hours and another clamp with Intralipid/heparin infusion was performed after 1 week. Tissue biopsies were performed before and after each clamp. Results: Overweight/obese subjects had higher AT DIO2, DIO3, and NCOR1, lower AT THRA and PPARGC1A, higher SM NCOR1, and lower SM DIO2, DIO3, PPARGC1A, and ATP2A2 expression. In AT, DIO2 and PPARGC1A increased, whereas NCOR1 and FOXO1 decreased after the clamp only in normal weight individuals. DIO3 decreased in both groups. In SM, NCOR1 decreased, whereas PPARGC1A and ATP2A2 increased after the clamp only in normal weight individuals. Tissue THRA and THRB decreased in both groups. Intralipid/heparin abolished these effects. Conclusions: Alterations in AT and SM expression of TH-related gene indicate a decreased tissue TH action in obesity. Inability to increase TH-related gene expression in obesity and during FFA oversupply may contribute to the aggravation of lipotoxicity.

The impact of metformin on hypothalamic-pituitary-thyroid axis activity in postmenopausal women with untreated non-autoimmune subclinical hypothyroidism.

Metformin was found to reduce elevated thyrotropin levels in subjects with hypothyroidism. The impact on thyrotropin levels was stronger in women receiving oral contraceptive pills than in women not using any contraception. The aim of the present study was to determine whether physiological levels of oestradiol determine the effect of metformin on hypothalamic-pituitary-thyroid axis activity. The study population included 40 postmenopausal women with prediabetes and untreated non-autoimmune subclinical hypothyroidism, using (group A; n=18) or not using (group B; n=22) oestradiol replacement therapy. Over the entire study periods, all subjects were treated with metformin (2.55-3.00g daily). Plasma levels of glucose, lipids, insulin, thyrotropin, free thyroxine, free triiodothyronine, prolactin, gonadotropins and oestradiol were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning of the study and 6months later. At entry, both groups differed in gonadotropin and oestrogen levels. Despite improving insulin sensitivity, thyrotropin levels and Jostel's thyrotropin index in both study groups, these effects were stronger in group A than group B. Only in group A, metformin increased SPINA-GT, while only in group B the drug decreased FSH levels. Levels of the other variables remained at a similar level throughout the study. The effect of treatment on thyrotropin levels correlated with its baseline values, as well as with the improvement of insulin sensitivity. The results obtained suggest that the impact of metformin on hypothalamic-pituitary-thyroid axis activity depends on the oestrogen status of patients.

Lactation improves pancreatic β cell mass and function through serotonin production.

Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for years after the cessation of lactation. We analyzed metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. Lactating and non-lactating women showed comparable glucose tolerance at 2 months after delivery, but after a mean of 3.6 years, glucose tolerance in lactated women had improved compared to non-lactated women. In humans, the disposition index, a measure of insulin secretory function of β cells considering the degree of insulin sensitivity, was higher in lactated women at 3.6 years after delivery. In mice, lactation improved glucose tolerance and increased β cell mass at 3 weeks after delivery. Amelioration of glucose tolerance and insulin secretion were maintained up to 4 months after delivery in lactated mice. During lactation, prolactin induced serotonin production in β cells. Secreted serotonin stimulated β cell proliferation through serotonin receptor 2B in an autocrine and paracrine manner. In addition, intracellular serotonin acted as an antioxidant to mitigate oxidative stress and improved β cell survival. Together, our results suggest that serotonin mediates the long-term beneficial effects of lactation on female metabolic health by increasing β cell proliferation and reducing oxidative stress in β cells.

The impact of oral hormonal contraception on metformin action on hypothalamic-pituitary-thyroid axis activity in women with diabetes and prediabetes: A pilot study.

The impact of metformin on thyrotropin levels is sex-dependent. No previous study has assessed whether sex steroids determine metformin action on thyrotrope and thyroid cell functioning. The aim of the present study was to compare the effect of this agent on hypothalamic-pituitary-thyroid axis activity and thyroid function tests between women receiving oral contraceptive pills and women not using any contraception. The study population included 52 women with subclinical hypothyroidism and prediabetes or diabetes, 20 of whom had been using oral contraceptive pills for at least 12months before the beginning of the study. Over the entire study period (4months), all participants received oral metformin (1.7-3g daily). Circulating levels of glucose, insulin, thyrotropin, free thyroid hormones, oestradiol, gonadotropins and prolactin were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning and at the end of the study. The study groups differed in oestradiol, gonadotropins and prolactin levels and in structure parameter inference approach (SPINA)-GT. In both groups, metformin reduced glucose levels, homeostasis model assessment 1 of insulin resistance index (HOMA1-IR), thyrotropin levels and Jostel's thyrotropin index, as well as increased SPINA-GT. In women receiving oral contraceptive pills, the drug slightly decreased serum prolactin levels. The impact on metformin on HOMA1-IR, thyrotropin, prolactin, Jostel's thyrotropin index and SPINA-GT was more pronounced if women received oral contraception, as well as more pronounced in patients treated with higher doses of this agent. Treatment-induced changes in thyrotropin and Jostel's thyrotropin index correlated with their baseline values, baseline levels of oestradiol and gonadotropins, as well as with the degree of a reduction in HOMA1-IR. This study is the first one to have shown that oral oestrogens potentiate the effect of metformin on hypothalamic-pituitary-thyroid axis activity.

The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study.

The effect ofmetforminon thyrotrope function seems to be sex dependent. The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on hypothalamic-pituitary-thyroidaxis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age, weight, insulin sensitivity, and thyrotropin levels. The first group (n = 11) included subjects with low serum testosterone levels, while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated withmetformin(2550-3000 mg daily). Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and freethyroidhormones were measured, while thestructure parameters of thyroid homeostasisand the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformindecreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel's thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel's index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.

Cardiometabolic Risk Factors in Men with Elevated Macroprolactin Content: A Pilot Study.

Macroprolactinemia is a condition associated with the presence of large amounts of high molecular weight complexes of prolactin. Despite high prevalence, clinical significance of macroprolactin remains poorly understood. The aim of this study was to assess cardiometabolic risk in men with isolated macroprolactinemia. The study population included 11 men with isolated macroprolactinemia, 14 subjects with monomeric hyperprolactinemia and 14 men with prolactin levels within the reference range. Glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D were determined in all included patients. Compared to healthy counterparts, men with isolated macroprolactinemia had higher levels of 2-h postchallenge glucose, hsCRP and fibrinogen, lower levels of 25-hydroxyvitamin D and reduced insulin sensitivity. Patients with monomeric hyperprolactinemia were characterized by increased plasma levels of 2-h postchallenge glucose, triglycerides, uric acid, hsCRP, fibrinogen and homocysteine, reduced insulin sensitivity and decreased plasma concentrations of HDL cholesterol and 25-hydroxyvitamin D. Subjects with isolated macroprolactinemia differed from patients with monomeric hyperprolactinemia in postchallenge plasma glucose, insulin sensitivity, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D. In men with monomeric hyperprolactinemia, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D, while in men with elevated levels of macroprolactin, uric acid, hsCRP, fibrinogen and 25-hydroxyvitamin D correlated with a content of monomeric prolactin or macroprolactin, respectively, as well as with a degree of insulin sensitivity. The obtained results suggest that macroprolactinemia may increase cardiometabolic risk but to a lesser extent than monomeric hyperprolactinemia.

β-Cell-Derived Angiopoietin-1 Regulates Insulin Secretion and Glucose Homeostasis by Stabilizing the Islet Microenvironment.

Islets are highly vascularized for prompt insulin secretion. Although angiopoietin-1 (Ang1) is a well-known angiogenic factor, its role in glucose homeostasis remains largely unknown. The objective of this study was to investigate whether and how Ang1 contributes to glucose homeostasis in response to metabolic challenge. We used inducible systemic Ang1 knockout (Ang1sys-/-) and β-cell-specific Ang1 knockout (Ang1β-cell-/-) mice fed a high-fat diet for 24 weeks. Although the degree of insulin sensitivity did not differ between Ang1sys-/- and Ang1sys+/+ mice, serum insulin levels were lower in Ang1sys-/- mice, resulting in significant glucose intolerance. Similar results were observed in Ang1β-cell-/- mice, suggesting a critical role of β-cell-derived Ang1 in glucose homeostasis. There were no differences in β-cell area or vasculature density, but glucose-stimulated insulin secretion was significantly decreased, and PDX-1 expression and GLUT2 localization were altered in Ang1β-cell-/- compared with Ang1β-cell+/+ mice. These effects were associated with less pericyte coverage, disorganized endothelial cell ultrastructure, and enhanced infiltration of inflammatory cells and upregulation of adhesion molecules in the islets of Ang1β-cell-/- mice. In conclusion, β-cell-derived Ang1 regulates insulin secretion and glucose homeostasis by stabilizing the blood vessels in the islet and may be a novel therapeutic target for diabetes treatment in the future.

Differences in β-cell function and insulin secretion in Black vs. White obese adolescents: do incretin hormones play a role?

Black youth are at higher risk for type 2 diabetes (T2D) than their White peers. Previously we demonstrated that for the same degree of insulin sensitivity, Black youth have an upregulated β-cell function and insulin hypersecretion, in response to intravenous (iv) glucose, compared with Whites. To investigate if the same holds true during an oral glucose challenge and because of the important role of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in augmenting insulin secretion, we examined β-cell function and incretin hormones in 85 Black and 78 White obese adolescents, with normal glucose tolerance (NGT), during a 2-h oral glucose tolerance test (OGTT) with mathematical modeling of plasma glucose and C-peptide concentrations to assess β-cell glucose sensitivity (βCGS), rate sensitivity, potentiation factor, and insulin sensitivity. Incretin, pancreatic polypeptide, and glucagon concentrations were measured during the OGTT. Black obese youth had a heightened early insulin secretion together with significantly greater βCGS, rate sensitivity, and potentiation factor compared with Whites, with no differences in incretin and glucagon concentrations. Basal and stimulated insulin clearance was lower (p = 0.001) in Black vs. White youth. In conclusion, during an OGTT Black obese youth with NGT demonstrate a pronounced early insulin secretion jointly with heightened β-cell glucose sensitivity, rate sensitivity, and potentiation factor. These racial disparities in β-cell function and the pathophysiological components of T2D are unlikely to be attributed to incretin hormones and remain to be investigated further to explain the metabolic basis for the enhanced risk of T2D in back youth.

The Effects of Bariatric Surgery-Induced Weight Loss on Adipose Tissue in Morbidly Obese Women Depends on the Initial Metabolic Status.

Adipose tissue (AT) dysfunction in obesity is commonly linked to insulin resistance and promotes the development of metabolic disease. Bariatric surgery (BS) represents an effective strategy to reduce weight and to improve metabolic health in morbidly obese subjects. However, the mechanisms and pathways that are modified in AT in response to BS are not fully understood, and few information is still available as to whether these may vary depending on the metabolic status of obese subjects. Abdominal subcutaneous adipose tissue (SAT) samples were obtained from morbidly obese women (n = 18) before and 13.3 ± 0.37months after BS. Obese women were stratified into two groups: normoglycemic (NG; Glu < 100mg/dl, HbA1c <5.7%) or insulin resistant (IR; Glu 100-126mg/dl, HbA1c 5.7-6.4%) (n = 9/group). A multi-comparative proteomic analysis was employed to identify differentially regulated SAT proteins by BS and/or the degree of insulin sensitivity. Serum levels of metabolic, inflammatory, and anti-oxidant markers were also analyzed. Before surgery, NG and IR subjects exhibited differences in AT proteins related to inflammation, metabolic processes, the cytoskeleton, and mitochondria. BS caused comparable weight reductions and improved glucose homeostasis in both groups. However, BS caused dissimilar changes in metabolic enzymes, inflammatory markers, cytoskeletal components, mitochondrial proteins, and angiogenesis regulators in NG and IR women. BS evokes significant molecular rearrangements indicative of improved AT function in morbidly obese women at either low or high metabolic risk, though selective adaptive changes in key cellular processes occur depending on the initial individual's metabolic status.

New evidence for an association between liver enzymes and pancreatic islet β-cell dysfunction in young obese patients

To explore the relationship between serum liver enzymes and both the glucose tolerance status and insulin secretion in young obese patients. A total of 734 young obese patients (BMI ≥ 25 kg m(-2)) and 231 lean healthy volunteers matched in age (BMI < 23 kg m(-2)) were enrolled in this cross-sectional observational study. The 734 obese patients were subdivided to three groups (OB-NGR, OB-IGR, and OB-DM) according to their glucose tolerance status. FSIVGTT was performed to assess the degree of insulin sensitivity (SI) and islet secretion function (AIRg). The disposition index (DI; product of SI and AIRg) was calculated as an integrated measurement of insulin secretion and insulin action after compensating for insulin resistance. The extent and distribution of hepatic fat infiltration was assessed using the liver/spleen ratio (L/S ratio) with CT scan. ALT and GGT levels in OB-NGR, OB-IGR, and OB-DM groups were significantly increased compared to the normal controls, and were incrementally increased in turn in the three groups, whereas DI decreased at the same time. One standard deviation increment in ALT and GGT increased the risk of β-cell dysfunction after controlling for potential confounders such as sex, age, BMI, waist-hip ratio, and blood pressure. Even after the adjustment of the serum lipid profile and L/S ratio, the odds ratio of ALT remained statistically significant (OR, 1.603; 95 % CI, 1.225-2.096). Serum levels of liver enzymes showed an independent close relationship with insulin secretion capacity. Excluding the impact of a fatty liver, increased ALT and GGT levels indicated a significant association with the attenuation of pancreatic β-cell function. This study provides the possibility that elevated liver enzymes might be treated as simple biomarkers of early insulin secretion deficit in type 2 diabetes, especially in young obese patients.

Stevioside Potentiates Insulin Sensitivity by Elevating Insulin-Stimulated Glucose Uptake in 3T3-L1 Adipocytes

Stevia rebaudiana Bertoni is a herb common to tropical and subtropical regions particularly Asia and South America. In countries like Malaysia, the sweet leaves of this plant have been used in daily cooking and as a form of alternative therapy by communities practicing folk medicines. The zero-calorie value of stevia leaves also provide a beneficial sweetening alternative to patients with metabolic syndromes like diabetes and obesity. A cell culture model of 3T3-L1 pre-adipocytes was implemented in this study to investigate the effects of stevioside, a major component extracted from the S. rebaudiana Bertoni plant on improving insulin sensitivity. 3T3-L1 pre-adipocytes were first differentiated to mature adipocytes prior to tests. The differentiation process was later confirmed by performing Oil Red-O staining. The degree of insulin sensitivity was measured by performing counts via the radioactive 2-deoxy-(1- 3 H)-glucose uptake assay. A separate assay was done to estimate the optimum insulin concentration in the glucose uptake of the 3T3-L1 adipocytes. Cells treated with stevioside showed significant increase in glucose uptake at lower concentrations compared to a diabetic drug, rosiglitazone maleate at higher concentrations of the compound. The enhancement of glucose uptake was 2.08-fold (p<0.001) in the cells treated with 30µM stevioside. Stevioside was thus seen to elevate insulin-stimulated glucose uptake concomitant with potentially enhanced insulin signaling in the 3T3-L1 cell culture model.

The Impact of Leptin and Adiponectin on Incident Type 2 Diabetes Is Modified by Sex and Insulin Resistance

Adiponectin and leptin and their ratio have been associated with incident type 2 diabetes (T2DM), although the data presented are conflicting and the populations studied have been small. In this large, prospective, nested, case referent study, we hypothesized that these associations are sex specific and may be modified by insulin resistance. Men and women aged 30-60 years with incident T2DM (n=640) and a prior health survey within the Västerbotten Intervention Programme (VIP) and matched referents (n=1564) were identified. Using conditional logistic regression analyses, we tested whether baseline plasma adiponectin and leptin levels and their ratio independently predicted incident T2DM, stratified for gender and insulin resistance. Adjusted for traditional risk factors, fourth-quartile levels of adiponectin were associated with a reduced risk of T2DM in men [odds ratio (OR) 0.55 (0.36-0.86)] and women [OR 0.47 (0.27-0.83)]. Quartile four of the leptin/adiponectin ratio predicted T2DM in both men [OR 3.08 (1.68-5.67)] and women [OR 3.31 (1.56-7.03)], whereas quartile-four levels of leptin predicted T2DM only in men [OR 2.30 (1.32-4.02)]. When stratified for insulin sensitivity and adjusted for body mass index (BMI), log(e)-transformed leptin predicted T2DM in insulin-sensitive men [OR 1.56 (1.13-2.17)] but not in insulin-resistant men [OR 1.03 (0.76-1.39)]. The effect of adiponectin and the leptin/adiponectin ratio was not influenced by the insulin sensitivity status. Leptin in men and adiponectin in both sexes were independent predictors of T2DM. The association was modified by the degree of insulin sensitivity. The leptin/adiponectin ratio may add predictive information beyond the separate hormones.

Comment on "The Changes of Blood Glucose Control and Lipid Profiles after Short-Term Smoking Cessation in Healthy Males"

Sir, Lee et al.1 reported the interesting finding that smoking cessation in healthy males was associated with a significant increase of insulin resistance, and speculated that the increase of the body weight following smoking cessation might contribute to the worsening of insulin resistance. They dealt with a small number of subjects and the follow-up period was only 2-months. As opposite results, they cited one report of increase of insulin resistance in 63 normoglycaemic smokers as compared to 21 non-smokers and 35 former smokers with normoglycaemia.2 Cena et al.3 suggest that nicotine, carbon monoxide, and other metabolites derived from nicotine may play important roles in insulin resistance. On this point, Eliasson et al.4 reported that the degree of insulin sensitivity was negatively correlated with the extent of nicotine use, as measured by the plasma cotinine level, in long-trem nicotine gum users (n=20, r=-0.469, p=0.034). In order to clarify these associations, the salivary cotinine and nicotine concentrations of 180 male smokers were measured. The mean age±standard deviation (range) of the subjects was 42.8±6.2 (33-58). Subjects at a workplace with a current history of treatment for diabetes and/or subjects whose fasting plasma glucose level was ≥140 mg/dL were excluded from the analysis. Sampling of saliva was conducted using Salisoft® (Assist Co. Ltd., Tokyo). The analyses were performed by high-performance liquid chromatography using CAPCELL PAK MG II C18 (Shiseido Co. Ltd., Tokyo) columns under the 195temperature of 50℃ and wavelength of 262 nm. The detection limits for nicotine and cotinine were 5 ng/mL and 10 ng/mL, respectively. As an indicator of insulin resistance, the homeostasis model assessment for insulin resistance (HOMA-IR)5 was calculated as follows: HOMA-IR=(Fasting plasma glucose×Fasting serum insulin)/405. Units of glucose and insulin used for the calculation of HOMA-R were mg/dL and µIU/mL, respectively. Bernert et al.6 reported a regression line of salivary cotinine against the serum cotinine as Log10 (salivary cotinine)=0.963×Log10 (serum cotinine)+0.127, with the square value of the correlation coefficient of 0.997. The main finding was that the log-transformed salivary cotinine and log-transformed salivary nicotine concentrations had no significant relationship with the log-transformed HOMA-IR. The partial correlation coefficients after adjustments for the age and body mass index were -0.056 for salivary cotinine and -0.047 for salivary nicotine, respectively. Thus, it was found using biological indicators of tobacco use, that the relationship between smoking and insulin resistance was weak after adjustment for age and body mass index. Although HOMA-IR is only a substitute indicator of insulin resistance ideally determined by the glucose clamp method, which was adopted by Eliasson et al.4 it is a simple and reliable method to detect insulin resistance in subjects without insulin depletion or insulin treatment. Numerous factors can affect insulin resistance, and I recommend that the net effect of smoking on insulin resistance should be examined in further detail.

Omental Gene Expression of Adiponectin Correlates with Degree of Insulin Sensitivity Before and After Gastric Bypass Surgery

Omental Gene Expression of Adiponectin Correlates with Degree of Insulin Sensitivity Before and After Gastric Bypass Surgery

Omental Gene Expression of Adiponectin Correlates with Degree of Insulin Sensitivity Before and After Gastric Bypass Surgery

Circulating adiponectin is known to correlate negatively with insulin resistance in patients with obesity and diabetes. The aim of this study was to assess the effect of gastric bypass (GB) surgery on adiponectin gene expression in subcutaneous and omental adipose tissues. Adipose tissues and plasma were obtained from 25 subjects undergoing GB surgery, 15 non-obese subjects, and 12 subjects after GB surgery. Real-time quantitative reverse transcription polymerase chain reaction was used for analysis of the adipose tissues. Adiponectin expression was normalized for glyceraldehyde 3-phosphate dehydrogenase and expressed as percentage of subject-matched subcutaneous expression which was given an arbitrary value of 100%. Insulin resistance was assessed by the homeostatic model assessment (HOMA). Circulating adiponectin was assayed by ELISA. Omental adiponectin gene expression was fivefold higher in subjects after GB when compared with age-matched morbidly obese subjects before GB (P < 0.01). There were no statistical differences in omental adiponectin gene expression observed in subjects after GB and age-matched non-obese subjects. For the entire cohort of subjects, there was a significant negative correlation between omental adiponectin expression and insulin resistance expressed by HOMA values (r = -0.62, P < 0.001). Circulating adiponectin was significantly lower (P < 0.05) in the obese group than in the non-obese and post-GB groups. Omental adiponectin gene expression significantly increases after GB surgery reaching levels equal to age-matched non-obese subjects. Omental adiponectin expression has a significant negative correlation with the insulin resistance status.