Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents

ContextIrisin, a novel exercise-induced myokine, has been suggested to regulate energy metabolism.ObjectiveWe studied the relationship between circulating irisin and metabolic and metabolite profiles of Korean adolescents, and investigated the effects of physical activity, obesity, and metabolic syndrome (MetS) on irisin levels.Materials and MethodsData were obtained from the Korean Children–Adolescents Study. Our cross-sectional study included 618 adolescents (370 normal-weight and 248 obese adolescents; 316 boys and 302 girls) aged 12–15 years. Body composition was determined using an impedance body composition analyzer and general participant characteristics and lifestyle information were obtained from questionnaires. Serum irisin levels were measured using a commercial kit.ResultsMean body mass index (BMI) was 19.4 kg/m² in normal-weight adolescents and 31.4 kg/m² in obese adolescents. Circulating irisin was positively correlated with adiposity indices, including BMI z-score, waist circumference, percent body fat, fat mass, fat-free mass, fat mass to fat-free mass ratio, and lipid and glucose metabolism markers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, insulin, and homeostasis model assessment-estimated insulin resistance (all p ≤ 0.006). Of these, increased body fat mass [standardized (Std) ß, 0.23; p < 0.0001], LDL-C (Std ß, 0.14; p = 0.0005) and fasting glucose (Std ß, 0.08; p = 0.0383) were the main independent factors associated with higher irisin levels. Moreover, elevated serum irisin was associated with the risk of obesity [odds ratio (OR], 2.2; confidence interval (CI), 1.19–3.87] and MetS (OR, 2.0; CI, 1.15–3.47). Furthermore, irisin and branched-chain amino acids were positively associated (p < 4 × 10^− 4 for Bonferroni correction). Additionally, in the normal-weight group, girls had higher irisin levels than boys (p = 0.006) and adolescents who engaged in regular physical activity had higher levels of irisin than sedentary adolescents (p = 0.0388). The relationship between physical activity and irisin levels was not observed in obese adolescents.ConclusionsElevated serum irisin was independently associated with the risk of obesity and positively correlated with unhealthy metabolic parameters and metabolites. Moreover, irisin levels were higher in active versus sedentary adolescents in the normal-weight group, but not in the obese group. Our findings suggest that irisin plays an important role in metabolic disorders and may be affected by physiopathological status.     

Reduced serum resistin levels in diabetic patients: Study from western India

ObjectiveResistin is an adipocyte-derived peptide that might play a role in obesity and insulin resistance (IR); however, its role in humans is largely unknown. The aim of the study was to elucidate the role of serum resistin and explore its relationship with inflammatory marker C-reactive protein (CRP) and adipocytokine (leptin, adiponectin) in Indian diabetic patients.Design and methodsA total of 171 subjects including 41 controls, 41 obese and 89 Type 2 diabetes mellitus (T2DM) patients were recruited in this cross-sectional study. Fasting serum resistin, leptin, adiponectin, insulin and CRP were measured by enzyme immunoassay. The relation between these variables was studied by univariate and multiple regression analysis.ResultsSerum resistin levels were significantly reduced in non-obese treated T2DM patients. In the correlation analysis after controlling for age and BMI we found that resistin is significantly associated with leptin (0.687, p < 0.002) and CRP (0.549, p < 0.018) in only control females and with CRP (0.642, p < 0.01) in T2DM female patients. In multiple linear regression analysis resistin was independently predicted by the leptin (p < 0.01) and leukocyte (p < 0.004) in controls, treated T2DM patients.ConclusionReduced resistin and leptin levels in non-obese treated T2DM and significant association between these two in control and treated T2DM suggest interplay between these two adipocytokines. In addition, the weak association of resistin with diabetes indicates that it may be playing an indirect role in the pathogenesis of T2DM.     

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

ObjectiveWeight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain.Materials/MethodsInsulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and was re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n = 73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2).ResultsAfter a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR ≥ 2.5) compared with only 25% of patients who maintained the weight loss (p = 0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio = 4.2; p = 0.039).ConclusionsCirculating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis.     

Lower circulating irisin is associated with type 2 diabetes mellitus

AimsIrisin is a novel myokine secreted in response to PPAR-γ co-activator-1α (PGC-1α) activation. Earlier studies suggested that PGC-1α expression and activity were lower in myocytes in type 2 diabetes mellitus (T2DM). Therefore, we hypothesize that circulating irisin levels are lower in T2DM patients.MethodsIn this observational study, we recruited 96 T2DM subjects and 60 non-diabetic control subjects. Among T2DM subjects, 38% were on insulin treatment, 78% were taking statins and 72% were taking renin-angiotensin system antagonists. Circulating irisin was quantified by ELISA and its association with markers of metabolic phenotype was analyzed by Pearson bivariate correlation and multiple linear regression.ResultsCirculating irisin was significantly lower in individuals with T2DM compared with non-diabetic controls (T2DM 204 ± 72 ng/ml vs. non-diabetic control 257 ± 24 ng/ml, p < 0.0001). In non-diabetic subjects, circulating irisin was correlated with age (r = 0.398, p < 0.01), BMI (r = 0.387, p < 0.01), total cholesterol (r = 0.341, p < 0.01), total triglycerides (r = 0.299, p < 0.05), fasting blood glucose (r = 0.430, p < 0.01) and diastolic blood pressure (r = 0.306, p < 0.05). Multiple linear regression model revealed that BMI (β = 0.407, p = 0.012) and FBG (β = 0.315, p = 0.034) were associated with irisin in non-diabetic subjects after adjusting for multiple co-variates. However, similar analysis in T2DM subjects didn’t reveal significant association between circulating irisin and major markers of metabolic phenotype.ConclusionsCirculating irisin is lower in T2DM compared with non-diabetic controls. Plasma irisin levels appear to be associated with important metabolic factors in non-diabetic subjects but not in individuals with type 2 diabetes.     

Common single nucleotide polymorphisms in the FNDC5 gene are associated with glucose metabolism but do not affect serum irisin levels in Japanese men with low fitness levels

ObjectiveThis cross-sectional study analyzed the association of serum irisin concentrations with cardiorespiratory fitness levels and common single nucleotide polymorphisms (SNPs) in the FNDC5 gene and examined the relationships between cardiorespiratory fitness levels, common SNPs in FNDC5, and glucose metabolism.Materials/MethodsCardiorespiratory fitness was assessed by measuring peak oxygen uptake (VO₂peak) and serum irisin levels by ELISA in 163 Japanese men (age, 21–79 years). Subjects were divided into low- and high-fitness groups within each age group according to the median VO₂peak value. Common SNPs (rs3480 and rs16835198) of the FNDC5 gene were genotyped with the TaqMan assay. Glucose metabolism was evaluated by measuring HbA1c, fasting plasma glucose (FPG), insulin levels, and HOMA-IR.ResultsSerum irisin levels were negatively correlated with age (p < 0.001) and not associated with the VO₂peak or HOMA-IR. In the low-fitness group, SNP analysis revealed that subjects with the rs3480 AG and GG genotypes had higher levels of insulin and HOMA-IR than those with the AA genotype (p < 0.01; no significant difference was observed in the high-fitness group). The GG genotypes of rs16835198 were associated with increased HbA1c and FPG in the low-fitness group only (p < 0.05). SNPs and both fitness groups were not associated with serum irisin levels.ConclusionsIn Japanese men, cardiorespiratory fitness levels and common SNPs in FNDC5 are not associated with circulating irisin levels, whereas high cardiorespiratory fitness abolishes the association between the rs3480 and rs16835198 SNPs and glucose metabolism independent of serum irisin levels.     

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism.Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75 g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 μmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT.ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.     

Increased systemic and adipose tissue inflammation differentiates obese women with T2DM from obese women with normal glucose tolerance

IntroductionObesity is strongly related to type-2 diabetes (T2DM), but there is a subset of obese individuals that remains relatively insulin sensitive and metabolically healthy. This study determined to what extent differences in metabolic health in obese women are associated with differences in adipose tissue and/or systemic inflammation.MethodsThe subject group consisted of age comparable lean (n = 12) and obese women either with T2DM (n = 28) or normal glucose tolerance (NGT; n = 26). Number of crown like structures (CLS) and adipocyte size were measured in subcutaneous and visceral adipose tissue of the obese women. Circulating cytokine and free fatty acid (FFA) levels, as well as number and activation status of peripheral leukocytes were determined.ResultsObese T2DM subjects showed higher circulating levels of IL-6, FFA and glycerol as compared to obese NGT subjects. Obese T2DM subjects had higher absolute numbers of peripheral leukocytes which were mainly due to an increase of T helper cells. Activation status of circulating cytotoxic T (CD8+CD25 +) and B (CD19+CD38 +) cells was significantly increased in obese NGT subjects as compared to lean but was not different between the two obese groups. Subcutaneous adipose tissue of obese T2DM subjects contained more CLS than adipose tissue of obese NGT subjects.ConclusionObese T2DM subjects show higher FFA levels and adipose tissue macrophage infiltration in addition to higher levels of circulating IL-6 and numbers of CD4 + T cells than obese NGT subjects. Hence, obese T2DM subjects show a higher extent of inflammation at both the systemic and adipose tissue level.     

Habitual shortened sleep and insulin resistance: An independent relationship in obese individuals

ObjectiveShort sleep duration has been reported to be associated with obesity, type 2 diabetes, and pre-diabetes. Since excess weight, glucose abnormalities, and insulin resistance tend to cluster, the individual role insulin resistance may have in habitual shortened sleep is unclear. The study purpose was to assess whether habitual sleep curtailment is independently related to insulin resistance in obese individuals.Materials/MethodsNon-diabetic, overweight/obese individuals from the community were stratified as insulin-resistant (n = 35) or insulin-sensitive (n = 21) based on steady-state plasma glucose concentrations (SSPG) during the insulin suppression test. Seventy-five gram oral glucose tolerance tests were performed. Participants were asked, “On average, how many hours of sleep do you get per night?” Shortened sleep duration was defined as less than 7 h of sleep per night.ResultsSSPG concentrations differed 2.5-fold (P < 0.001) between insulin-resistant and insulin-sensitive individuals. Impaired fasting glucose and glucose intolerance were prevalent in both groups (> 40%); however, body mass index, waist circumference, mean fasting or 2-h post-glucola glucose concentrations were not significantly different. Insulin-resistant individuals reported (mean ± SD) fewer hours of sleep than did insulin-sensitive individuals (6.53 ± 1.1 vs 7.24 ± 0.9 h, P < 0.05). Shortened sleep duration was more prevalent among insulin-resistant as compared with insulin-sensitive individuals (60% vs 24%, P < 0.05).ConclusionsNon-diabetic, insulin-resistant individuals averaged fewer hours of sleep and were more likely to report shortened sleep duration as compared with similarly obese insulin-sensitive individuals. There appears to be an independent association between habitual shortened sleep and insulin resistance among obese, dysglycemic adults without diabetes.     

The association between ectopic fat in the pancreas and subclinical atherosclerosis in type 2 diabetes

AimsEvidence that pancreatic fat accumulation has a role in obesity, metabolic syndrome and type 2 diabetes mellitus (DM) is emerging. However, data on the influence of pancreatic steatosis on subclinical atherosclerosis are lacking.MethodsWe examined 198 patients with type 2 DM. Pancreatic computed tomography (CT) attenuations were assessed using CT imaging. Obesity was defined as BMI ≥ 25 kg/m² according to the Asian-specific BMI cut-offs. We defined pancreatic steatosis as pancreatic attenuations below median levels.ResultsThe pancreatic attenuations was significantly correlated with age (r = −0.302, p < 0.001), visceral fat area (r = −0.194, p = 0.006) and vascular stiffness (r = −0.242, p = 0.001). In the non-obese group (BMI < 25 kg/m²), pancreatic steatosis was associated with a higher prevalence of carotid artery plaque and vascular stiffness. In the non-obese group, patients with pancreatic steatosis, compared with those without, had an odds ratio (OR) of 3.1 (95% CI 1.2–8.1) for carotid atherosclerosis, after adjusting for age, gender and BMI. However, significant associations between pancreatic steatosis and atherosclerosis were not found in the obese group.ConclusionEctopic fat in the pancreas is strongly associated with carotid atherosclerosis in non-obese subjects with type 2 DM. This finding highlights the importance of pancreatic fat deposits related to a higher risk of cardiovascular disease, especially in non-obese subjects.     

Relationship between circulating irisin,renal function and body composition in type 2 diabetes

AimsChronic kidney disease (CKD) secondary to type 2 diabetes mellitus (T2DM) is associated with multifaceted energy dysmetabolism. We aim to study the relationship between renal function, body composition and irisin, the recently identified myokine which is involved in energy regulation, in T2DM.MethodsCirculating irisin and body composition were measured in 365 T2DM subjects across a wide range of renal function.ResultsCirculating irisin was significantly decreased in T2DM with renal insufficiency (77.4 ± 13.7 ng/ml in T2DM with eGFR ≥ 60 ml/min/1.73 m² versus 72.5 ± 14.9 ng/ml in those with eGFR < 60 ml/min/1.73 m², p = 0.001) and the reduction in irisin was most pronounced in stage 5 CKD patients. In T2DM with preserved renal function, irisin was correlated with age (r = − 0.242, p = 0.001) and pulse pressure (r = − 0.188, p = 0.002). Among those with renal insufficiency, irisin was correlated with BMI (r = 0.171, p = 0.022), fat mass (r = 0.191, p = 0.013), percentage of fat mass (r = 0.210, p = 0.007) and eGFR (r = 0.171, p = 0.020). Multivariate linear regression models revealed that variations in circulating irisin were mainly attributable to eGFR and age in T2DM with and without renal impairment, respectively.ConclusionOur observations suggest that the level of circulating irisin may be associated with renal function in T2DM. The role of reduced irisin in energy dysmetabolism in diabetic patients with renal insufficiency deserves further investigation.     

Autonomic function is not associated with the incidence of type 2 diabetes in a high-risk population: The Hoorn study

AimImpaired autonomic function is a complication of type 2 diabetes mellitus (DM2), but may also be involved in its development. For this reason, this study looked at the association of autonomic function with the incidence of DM2 in a homogeneous Caucasian population.MethodsThis Hoorn study was a prospective population-based study of individuals aged 50–75 years. For the 631 participants, the standard deviation of all normal-to-normal intervals (SDNN) and eight other parameters of autonomic function were calculated at baseline. Fasting and 2-h glucose were measured during follow-up by oral glucose tolerance test (OGTT). DM2 at baseline and follow-up was ascertained by questionnaire and OGTT. After excluding participants with DM2 at baseline, the association of parameters of autonomic function with incident diabetes was examined using logistic-regression analysis while adjusting for possible confounders.ResultsAfter excluding those with known (n = 67) or newly diagnosed (n = 126) DM2 at baseline and those missing follow-up data (n = 140), 298 participants were eligible for the study (182 with normal glucose tolerance, 19 with impaired fasting glucose and 97 with impaired glucose tolerance). During a median follow-up of 9.2 (range 4.5–11.1) years, 94 incident cases of DM2 were observed. After adjusting for confounding variables, the DM2 odds ratio was 1.12 (95% CI: 0.77, 1.64) per SDNN increase. Results for other parameters of autonomic function were similar.ConclusionThe present study found no evidence of an association between autonomic function and DM2 incidence in a population at high risk of diabetes. This implies that previously observed associations between autonomic function and glucose metabolism in cross-sectional settings may reflect reverse causation.     

Leptin as an important link between obesity and cardiovascular risk factors in men with acute myocardial infarction

ObjectiveThe levels of leptin, a major regulator of lipid metabolism, may increase in obesity, and contribute to the development of metabolic syndrome. Leptin is produced by adipose tissue and is a peptide hormone, which has strong association with obesity, elevated cardiovascular risk, and morbidity. The present study was designed to evaluate the relationships between leptin levels, obesity, and cardiovascular risk factors in men with acute myocardial infarction.Methods and resultsTwenty-four obese and twenty-three nonobese male patients, who had experienced their first myocardial infarction, were included in the study. Their leptin levels, biochemical parameters, and anthropometric measures were obtained. Mean leptin levels were significantly higher in the obese group compared to the nonobese group (2.53 ng/mL versus 1.23 ng/mL; p < 0.01). Leptin levels correlated positively with anthropometric measurements, triglyceride, fasting glucose, C-reactive protein, and uric acid levels, and negatively with high-density lipoprotein cholesterol levels.ConclusionFindings indicate high leptin levels to be positively correlated with obesity and diastolic blood pressure in male patients with myocardial infarction.     

Impact of body mass index and metabolic phenotypes on coronary artery disease according to glucose tolerance status

ObjectiveThis study aimed to examine the impact of obesity, as defined by body mass index (BMI), and a metabolically unhealthy phenotype on the development of coronary artery disease (CAD) according to glucose tolerance status.MethodsThis population-based retrospective cohort study included 123,746 Japanese men aged 18–72 years (normal glucose tolerance: 72,047; prediabetes: 39,633; diabetes: 12,066). Obesity was defined as a BMI ≥ 25 kg/m². Metabolically unhealthy individuals were defined as those with one or more of the following conditions: hypertension, hypertriglyceridaemia and/or low HDL cholesterol. A Cox proportional hazards regression model identified variables related to CAD incidence.ResultsThe prevalences of obese subjects with normal glucose tolerance, prediabetes and diabetes were 21%, 34% and 53%, whereas those for metabolically unhealthy people were 43%, 60% and 79%, respectively. Multivariate analysis showed that a metabolically unhealthy phenotype increases hazard ratios (HRs) for CAD compared with a metabolically healthy phenotype, regardless of glucose tolerance status (normal glucose tolerance: 1.98, 95% CI: 1.32–2.95; prediabetes: 2.91, 95% CI: 1.85–4.55; diabetes: 1.90, 95% CI: 1.18–3.06). HRs for CAD among metabolically unhealthy non-obese diabetes patients and obese diabetes patients with a metabolically unhealthy status were 6.14 (95% CI: 3.94–9.56) and 7.86 (95% CI: 5.21–11.9), respectively, compared with non-obese subjects with normal glucose tolerance and without a metabolically unhealthy status.ConclusionA metabolically unhealthy state can associate with CAD independently of obesity across all glucose tolerance stages. Clinicians may need to consider those with at least one or more conditions indicating a metabolically unhealthy state as being at high risk for CAD regardless of glucose tolerance status.     

The change in one-hour postload plasma glucose levels,and an analysis of its related factors in abdominally obese Han Chinese men with normal glucose tolerance

ObjectiveThis study was to observe the difference in one-hour postload plasma glucose levels and analyze its related factors in abdominally obese men with normal glucose tolerance (NGT).DesignThis case–control study included 36 abdominally obese men (waist circumference ≥ 90 cm) and 31 non-abdominally obese men (waist circumference < 90 cm) aged 20–50 years with NGT. Cases and controls were matched in age. All subjects underwent oral glucose tolerance test with 75 g of oral anhydrous glucose.Results0.5 and 1-h postload plasma glucose levels were higher in abdominally obese group than in non-abdominally obese group (P < .05). Fasting plasma glucose (FPG), 2 and 3-h postload plasma glucose were similar in the two groups (P > .05). 1-h postload plasma glucose was positively correlated with body mass index (r = 0.454), waist circumference(WC) (r = 0.519), systolic blood pressure (r = 0.456), diastolic blood pressure (r = 0.338), triglycerides (r = 0.439), and negatively correlated with high density lipoprotein cholesterol (r = ? 0.391), 1/fasting insulin (r = ? 0.459), insulinogenic index (r = ? 0.357) and disposition index (r = ? 0.602) (P < .01). In multiple regression analysis, 1-h postload plasma glucose maintained an independent association with disposition index (β = ? 1.367, P = .000), WC (β = 0.103, P = .000) and triglycerides (β = 0.185, P = .017).ConclusionsThe present study demonstrated that the level of one-hour postload plasma glucose was elevated in abdominally obese men with NGT. Besides FPG and 2-h postload plasma glucose, we must also pay attention to the measurement of one-hour postload plasma glucose. Disposition index, WC and triglycerides were independently related factors for elevated one-hour postload plasma glucose.     

SHBG levels correlate with insulin resistance in postmenopausal women

BackgroundOverweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance and has been identified as a target for new therapeutic strategies, including early change in lifestyle. Early biochemical markers for identifying at-risk patients will be useful for prevention studies. The aim of this study is to investigate whether or not SHBG level is a useful index of hyperinsulinemia and/or insulin resistance in pre- and postmenopausal obese women. At the same time, the relationship between SHBG concentrations and features of the metabolic syndrome were evaluated.Methods229 women were eligible for this study. MetS was defined by using a modification of the ATP III guidelines. All patients were euthyroid, obese and overweight, 25 to 69 years of age. Subjects were divided into groups of premenopausal women (n = 125) and postmenopausal women (n = 104). Various fatness and fat distribution parameters, SHBG, sex hormones, FSH, LH, thyroid hormones, serum levels of fasting and postprandial glucose, lipid profile, uric acid and serum insulin, and blood pressure were measured.ResultsNo significant difference was found in mean SHBG levels between pre- and postmenopausal obese women in this study (p = 0.866).In premenopausal obese women, SHBG correlated negatively with BMI, waist circumference, fasting glucose, uric acid levels and FAI.In postmenopausal obese women, SHBG correlated negatively with fasting glucose, postprandial plasma glucose, fasting insulin, HOMA-IR and FAI and positively with HDL.SHBG had a significant inverse association with MetS parameters only in postmenopausal women, also after adjusting for BMI, age and estradiol.ConclusionsObesity may influence the levels of endogenous sex steroid, especially after menopause. SHBG concentrations are correlated with features of the metabolic syndrome, particularly in postmenopausal obese women.These results suggest that SHBG may be an index of insulin resistance in postmenopausal obese women.     

Effects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: A post-hoc analysis of the BIGPRO1 trial

AimMetformin has recently been considered as a possible pharmacological complement to lifestyle measures for preventing type 2 diabetes in high-risk subjects. However, little is known of its effects on metabolic and cardiovascular risk factors in non-diabetic subjects.MethodsThe BIGPRO1 trial was a 1-year multicentre, randomized, double-blind, controlled clinical trial of metformin versus placebo, carried out in the early 1990s, in 457 upper-body obese non-diabetic subjects with no cardiovascular diseases or contraindications to metformin. We compared the changes (1-year minus baseline) in cardiometabolic risk factors between treatment groups in two subsets of trial subjects: those with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n = 101); and those who fulfilled the inclusion criteria of the Diabetes Prevention Program (DPP) (n = 51). Comparisons were adjusted for age and gender.ResultsIn the IFG/IGT subset, significant differences in 1-year changes were observed for systolic blood pressure, which decreased markedly more in the metformin group than in the placebo group (P < 0.003), and for fasting plasma glucose, and total and LDL cholesterol, which decreased slightly in the metformin group, but increased in the placebo group (P < 0.04). Similar results were observed in the subset with DPP criteria. Also, there were no significant differences in 1-year changes for weight, waist-to-hip ratio, 2-h post-load blood glucose, fasting and 2-h post-load insulin, HDL cholesterol, triglycerides and fibrinolytic markers between the two treatment groups.ConclusionIn subjects at high risk of developing diabetes, the use of metformin showed beneficial and no untoward effects on cardiometabolic risk factors.     

Early-stage atherosclerosis in newly diagnosed,untreated type 2 diabetes mellitus and impaired glucose tolerance

AimThe aim of this study was to investigate early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT).MethodsThe study subjects underwent an oral glucose tolerance test (OGTT) and were then divided into three groups, according to plasma glucose level: those in the normal glucose tolerance (NGT) group had fasting plasma glucose (FPG) < 6.1 mmol/L and 2 h postload glucose (2hPPG) < 7.8 mmol/L; those in the IGT group had FPG < 6.1 mmol/L and 2hPPG ≥ 7.8 mmol/L; and those in the T2DM group had FPG ≥ 7.0 mmol/L or 2hPPG ≥ 11.1 mmol/L. Haemodynamic variables and brachial–ankle pulse-wave velocities (baPWV) in the three groups were compared.ResultsThe baPWV value increased with increases in plasma glucose, and was significantly and positively correlated to age, FPG, 2hPPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference and waist-to-hip ratio. Significant differences were found between the baPWV values in the NGT and IGT groups (1602 ± 347 vs 1707 ± 351 cm/s, respectively; P = 0.005), and between the NGT and DM groups (1602 ± 347 vs 1762 ± 381, respectively; P < 0.001). The results of multiple regression analyses showed that 2hPPG was closely related to baPWV as well as to SBP and DBP.ConclusionEarly-stage atherosclerosis is present in newly diagnosed, untreated T2DM and IGT patients, and it may be that its early assessment, along with good control of hypertension and hyperglycaemia, will help to delay its progression.     

A large proportion of prediabetes and diabetes goes undiagnosed when only fasting plasma glucose and/or HbA1c are measured in overweight or obese patients

AimsThe purposes of the study were to determine the prevalence of unrecognized dysglycaemia in overweight (body mass index [BMI] 25–29.9 kg/m²) and obese (BMI ≥30 kg/m²) patients, to assess the extent to which measures of fasting plasma glucose (FPG) and/or HbA_1c, compared with oral glucose tolerance tests (OGTTs), misdiagnose dysglycaemia, and to determine the factors associated with an isolated abnormal post-OGTT glucose value.MethodsOGTT was performed and HbA_1c was measured in 1283 inpatients with BMI scores ≥25 kg/m² and no history of dysglycaemia.ResultsPrediabetes was found in 257 (20.0%) subjects (197 with impaired glucose tolerance, 29 with impaired fasting glucose, 31 with both) and diabetes in 77 (6.0%), including 22 with FPG ≥7 mmol/L (WHO definition). The sensitivity of FPG >6 mmol/L, FPG >5.5 mmol/L, HbA_1c ≥6% and the recommendations of the French National Agency of Accreditation and Evaluation in Health Care (ANAES) to identify patients with abnormal OGTTs was 29.9, 41.3, 36.8 and 15.6%, respectively. The factors that were independently associated with diabetes in obese women with FPG <7 mmol/L were age (per 10 years: OR 1.54 [1.00–2.11]; P = 0.049) and FPG (OR 6.1 [1.4–30.0]; P = 0.014), whereas age (OR 1.26 [1.09–1.44]; P < 0.01) and waist circumference (per 10 cm: OR 1.17 [1.01–1.33]; P < 0.05) were independently associated with dysglycaemia in obese women with FPG <6.1 mmol/L.ConclusionIn overweight and obese patients: dysglycaemia is commonly seen; FPG alone, compared with OGTT, failed to diagnose 70% of dysglycaemia cases; FPG >5.5 mmol/L and HbA_1c ≥6.0% are not necessarily substitutes for OGTT; and older age and larger waist circumference should be used to select those obese women with normal FPG who might further benefit from OGTTs to diagnose dysglycaemia.     

Adipocytokine profiles as influenced by insulin resistance in obese subjects

ObjectiveThis study aims to explore the baseline adipocytokine profiles of adult Saudis and evaluate their relationship in the development of insulin resistance.MethodsIn this cross-sectional study, 300 adult Saudis with varying glucose tolerance were recruited. They were grouped into NGT, IGT and DM. Anthropometrics, glucose and lipid profiles were analyzed by routine methods; leptin, adiponectin, resistin and CRP were measured by ELISA.ResultsInsulin resistance was significantly correlated with levels of CRP (R = 0.32, p = 0.02) in the NGT; with leptin levels (R = 0.46, p = 0.001) in the IGT; and with adiponectin levels (R = 0.25, p = 0.001) in all groups. In males, resistin and CRP exhibited significant correlations to insulin resistance (R = 0.33, p = 0.005); in females significant correlation was demonstrated between insulin resistance and adiponectin (R = 0.32, p = 0.003). Significant associations exist in the adipocytokine profiles of adults with different glucose tolerance.ConclusionCertain adipocytokines can be used not only as promising markers but also as potential adjunct therapy with regards to insulin sensitivity and obesity.     

A comparative study of insulin resistance for Saudi and Caucasian subjects across a range of glycaemic categories

AimSaudi and Caucasian subjects, matched for adiposity, and of differing glycaemic status were compared using several insulin sensitivity indices and to also to assess insulin, glucose and insulin-like growth factor binding protein-1 (IGFBP-1) responses to intravenous glucose.MethodsSubjects with normal glucose tolerance (NGT; n = 24), impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), and type 2 diabetes (DM; n = 13) were recruited from Saudi (n = 33) and Caucasian (n = 28) populations. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test (FSIVGTT) at a second visit.ResultsSaudis in the NGT and pooled glucose intolerance categories had significantly higher diastolic blood pressure (p < 0.001, p < 0.05 respectively) and HbA1c (p < 0.01, p < 0.05 respectively) compared to Caucasians. Caucasians in the NGT category had significantly higher Si, fasting and 2 h IGFBP-1 (p < 0.01, p < 0.05 and p < 0.01 respectively) compared to Saudis. Two hours following oral or intravenous glucose serum IGFBP-1 decreased to 44% (p < 0.001) and 50% (p < 0.05) of baseline levels respectively.ConclusionsOur data suggest that adult Saudis with normal glucose tolerance appear to be more insulin resistant than Caucasians matched for adiposity. In normal individuals at 2 h the IGFBP-1 level will be about half the baseline level regardless of the route of glucose administration.