Impact of diabetes on muscle mass, muscle strength, and exercise tolerance in patients after coronary artery bypass grafting

Background

The impact of diabetes mellitus (DM) on muscle mass, muscle strength, and exercise tolerance in patients who had undergone coronary artery bypass grafting (CABG) has not been fully elucidated.

Methods

We enrolled 329 consecutive patients who received cardiac rehabilitation (CR) after CABG (DM group, n = 178; non-DM group, n = 151) and measured lean body weight, mid-upper arm muscle area (MAMA), and handgrip power (HGP) at the beginning of CR. We also performed an isokinetic strength test of the knee extensor (Ext) and flexor (Flex) muscles and a cardiopulmonary exercise testing at the same time.

Results

No significant differences in risk factors, including age, gender, number of diseased vessels, or ejection fraction were observed between the 2 groups. The levels of Ext muscle strength, peak oxygen uptake, and anaerobic threshold were significantly lower in the DM group than in the non-DM group (all p < 0.05). Both peak oxygen uptake and MAMA correlated with Ext and Flex muscle strength as well as HGP (all p < 0.005). The MAMA, HGP, and Ext muscle strength were lower in patients who received insulin therapy than in those who did not. Interestingly, fasting glucose levels significantly and negatively correlated with Ext muscle strength.

Conclusions

These data suggest that DM patients had a lower muscle strength and exercise tolerance than non-DM patients. Moreover, a high glucose level may affect these deteriorations in DM patients after CABG.     

Prospective study of the impact of diabetes mellitus newly diagnosed by glycated hemoglobin on outcomes in patients undergoing percutaneous coronary intervention

BackgroundWe sought to determine the prevalence of diabetes mellitus (DM) newly diagnosed by elevated glycated hemoglobin (HbA1c) in patients undergoing percutaneous coronary intervention (PCI) and its association with 1-year clinical outcomes.MethodsWe prospectively enrolled consecutive patients undergoing PCI (2011–2013). HbA1c levels were assessed during the index hospitalization and newly diagnosed DM was defined as HbA1c ≥ 6.5% in the absence of the previous diagnosis. The primary outcome was MACCE (Major Adverse Cerebro- and Cardiovascular Events) defined as death, stroke, PCI or acute myocardial infarction at 1 year.ResultsDiabetes was previously diagnosed in 391 (34%) patients (DM group), 221 (19%) had newly diagnosed DM based on the HbA1c level and 539 (47%) did not have diabetes (Non-DM). In DM group HbA1c was 7.80 ± 1.36% as compared with 7.62 ± 1.30% in patients with newly diagnosed DM (p < 0.001). These patients were younger (62.0 ± 11.3 years) compared to DM (67.9 ± 10.4 years) and non-DM (63.7 ± 13.0) patients, p < 0.001. 1-year MACCE rates were 14.8%, 19.5% and 27.96% in the non-DM, newly diagnosed DM and DM groups, respectively (p < 0.001). Multivariate analysis showed that compared to non-DM, the adjusted one-year hazard ratios for MACCE were 1.75 and 1.40 in patients with known DM and newly diagnosed DM, respectively (p < 0.05 for both).ConclusionNewly diagnosed DM based on peri-procedural HbA1c is common and associated with increased short and long term risk for adverse outcomes. Our results may warrant routine screening for DM in all patients undergoing PCI.     

Implicaciones pronósticas de los índices fisiológicos coronarios en pacientes con diabetes mellitus

Introduction and objectivesNo thorough investigation has been performed of the prognostic value of coronary physiological indices in patients with diabetes mellitus (DM) after coronary revascularization deferral.MethodsWe analyzed 714 patients (235 with DM) with deferred revascularization according to fractional flow reserve (> 0.80). A comprehensive physiological evaluation including coronary flow reserve (CFR), index of microcirculatory resistance, and fractional flow reserve was performed at the time of revascularization deferral. The median values of the CFR (2.88), fractional flow reserve (0.88), and index of microcirculatory resistance (17.85) were used to classify patients into high- or low-index groups. The primary outcome was the patient-oriented composite outcome (POCO) at 5 years, comprising all-cause death, any myocardial infarction, and any revascularization.ResultsCompared with the non-DM population, the DM population showed higher risk of POCO (HR, 2.49; 95%CI, 1.64-3.78; P < .001). In the DM population, the low-CFR group had a higher risk of POCO than the high-CFR group (HR, 3.22; 95%CI, 1.74-5.97; P < .001). In contrast, CFR values could not differentiate the risk of POCO in the non-DM population. There was a significant interaction between CFR and the presence of DM regarding the risk of POCO (P for interaction = .025). Independent predictors of POCO were a low CFR and family history of coronary artery disease in the DM population and percent diameter stenosis and multivessel disease in the non-DM population.ConclusionsThe association between coronary physiological indices and clinical outcomes differs according to the presence of DM. In deferred patients, CFR is the most important prognostic factor in patients with DM, but not in those without DM.     

The comparison of resistance and balance exercise on balance and falls efficacy in older females

ObjectivesThe purpose of this study is to compare the effectiveness of resistance and balance exercise in reducing the risk of falls for females 65-years-old or older.DesignThe study was a single blind, controlled trial, conducted over a period of 12-weeks with pre- and post-exercise assessment.Patients and methodsNinety-five participants were randomly assigned to one of three groups: resistance-training group, balance training group, control group. Resistance training group were trained to increase strength of upper, lower. Balance training group were trained to improve balance, coordination and proprioception. Outcome measurement consisted of balance ability, muscle strength, proprioception and fall efficacy.ResultsThe resistance and balance exercise group showed a statistically significant improvement in balance ability compared to the control group (P < 0.01). The resistance exercise group showed significant improvement in muscle strength compared to the balance exercise group (P < 0.01). The balance exercise group showed significant improvement in proprioception compared to the resistance exercise group (P < 0.01). Both resistance and balance exercise showed a significant improvement in fall efficacy than the control group (P < 0.01).ConclusionsWe conclude that the resistance and balance exercise have significant effects on balance ability and falls efficacy in older females.     

Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes correlates with β-catenin accumulation

Aimsβ-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear.MethodsColorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1 year (n = 27) and non-DM patients without hyperglycemia (n = 20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n = 6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence.ResultsCompared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group (all p < 0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient = 0.55; p < 0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p < 0.01).ConclusionsEnhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes.     

Association of adiponectin with peripheral muscle status in elderly patients with heart failure

BackgroundReduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF.MethodsWe measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer.ResultsSerum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p < 0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p = 0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p = 0.006 and p < 0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength.ConclusionsOur findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients.     

Plaque stabilization by intensive LDL-cholesterol lowering therapy with atorvastatin is delayed in type 2 diabetic patients with coronary artery disease—Serial angioscopic and intravascular ultrasound analysis

BackgroundDiabetes mellitus (DM) is a major risk factor for cardiovascular events. The study purpose was to compare DM and non-DM (nDM) patients in terms of statin-induced change of plaque characteristics using intravascular ultrasound (IVUS) and coronary angioscopy.MethodsPatients with coronary artery disease and hypercholesterolemia who were enrolled to the TWINS were selected and classified into two groups: DM group and nDM group. Eleven DM patients and 28 nDM patients were studied.ResultsLow-density lipoprotein cholesterol levels decreased significantly to a similar extent at weeks 28 and 80 from baseline in DM and nDM (p < 0.001). The mean angioscopic color grades of yellow plaques in DM and nDM were similar at baseline and significantly decreased at week 80 from baseline in both groups, however, the mean change of angioscopic color grade from baseline in DM were not significantly decreased and the mean angioscopic color was significantly higher than that in nDM (1.34 vs. 1.00, p < 0.05) at week 28. IVUS showed plaque volume reduction in both groups (p < 0.01) except at week 80 in DM group, which was not statistically significant different compared to the baseline.ConclusionIn DM patients, plaque volume regression by atorvastatin was shown to be attenuated, and its color improvement was significantly delayed. However, the yellowness became comparable between DM and nDM groups at week 80. These results indicate that patients with DM should be treated by intensive lipid-lowering therapy with atorvastatin for at least 80 weeks to stabilize vulnerable plaque.     

Higher uric acid serum levels are associated with better muscle function in the oldest old: Results from the Mugello Study

BackgroundSarcopenia is the progressive loss of muscle mass and strength that occurs with advancing age and plays a pivotal role in the causal pathway leading to frailty, disability and, eventually, to death among older persons. As oxidative damage of muscle proteins has been shown to be a relevant contributory factor, in this study we hypothesized that uric acid (UA), a powerful endogenous antioxidant, might exert a protective effect on muscle function in the oldest old and we tested our hypothesis in a group of nonagenarians who participated in the Mugello Study.Methods239 subjects, 73 men and 166 women, mean age 92.8 years ± SD 3.1, underwent the assessment of UA serum level and isometric handgrip strength, a widely used clinical measure of sarcopenia.ResultsMean UA serum level was 5.69 mg/dL ± SD 1.70 and mean handgrip strength was 15.0 kg ± SD 6.9. After adjusting for relevant confounders, higher UA serum levels remained independent positive predictors of isometric handgrip strength (β 1.24 ± SE(β) 0.43, p = 0.005).ConclusionOur results show that higher UA serum levels are associated with better muscle function in the oldest old and, accordingly, might slow down the progression of sarcopenia.     

Exercise improves gait,reaction time and postural stability in older adults with type 2 diabetes and neuropathy

AimsFor older adults with type 2 diabetes (T2DM), declines in balance and walking ability are risk factors for falls, and peripheral neuropathy magnifies this risk. Exercise training may improve balance, gait and reduce the risk of falling. This study investigated the effects of 12 weeks of aerobic exercise training on walking, balance, reaction time and falls risk metrics in older T2DM individuals with/without peripheral neuropathy.MethodsAdults with T2DM, 21 without (DM; age 58.7 ± 1.7 years) and 16 with neuropathy (DM-PN; age 58.9 ± 1.9 years), engaged in either moderate or intense supervised exercise training thrice-weekly for 12 weeks. Pre/post-training assessments included falls risk (using the physiological profile assessment), standing balance, walking ability and hand/foot simple reaction time.ResultsPre-training, the DM-PN group had higher falls risk, slower (hand) reaction times (232 vs. 219 ms), walked at a slower speed (108 vs. 113 cm/s) with shorter strides compared to the DM group. Following training, improvements in hand/foot reaction times and faster walking speed were seen for both groups.ConclusionsWhile falls risk was not significantly reduced, the observed changes in gait, reaction time and balance metrics suggest that aerobic exercise of varying intensities is beneficial for improving dynamic postural control in older T2DM adults with/without neuropathy.     

Positive associations between serum levels of IGF-I and subcutaneous fat depots in young men. The Odense Androgen Study

IntroductionSerum levels of IGF-I are of growing interest due to the associations with morbidity and mortality. Despite markedly suppressed GH secretion, total IGF-I levels are often within normal range in obese adults.AimTo study associations between IGF-I and estimated muscle mass in the Odense Androgen Study population and secondly to investigate associations between serum IGF-I and regional fat depots.MethodThe Odense Androgen Study is a population-based, cross-sectional study of 776 randomly selected men aged 20–29 years. Regional lean and fat mass were measured by dual-energy X-ray absorptiometry, whereas regional muscle and fat areas were assessed by magnetic resonance imaging.ResultsAge-adjusted IGF-I levels correlated significantly with different estimates of muscle mass (r‐values between 0.15 and 0.19; p < 0.001). Using multiple linear regression, serum IGF-I correlated positively with subcutaneous adipose tissue on the abdomen (SAT) after controlling for visceral adipose tissue (VAT) in the whole group and in the subgroup of men with normal waist circumference (r-values between 0.13 and 0.15; p < 0.03). In addition, IGF-I correlated positively with subcutaneous thigh fat area (TFA) after controlling for intramyocellular lipid (imcl) r = 0.18; p < 0.004) and IGF-I correlated negatively with TFAimcl in the whole group and in the subgroup of men with normal waist circumference.ConclusionSAT and subcutaneous TFAs were positively associated with IGF-I in regression analyses. Conversely, imcl of the thigh was inversely associated with IGF-I levels. These findings emphasize the differential associations between IGF-I and regional fat deposits. Future studies may provide further insight regarding the interplay between circulating IGF-I levels and regional muscle and fat mass.     

Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2 diabetes

AimThis study assessed the impact of regular exercise on inflammatory markers (high-sensitivity C-reactive protein [hsCRP], fibrinogen), and matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), in patients with type 2 diabetes mellitus (T2DM).PatientsFifty overweight patients with T2DM were randomly assigned to two groups: (A) an exercise group (EXG, n = 25), with self-controlled exercise for at least 150 min/week and one additional supervised exercise session/week; and (B) a control group (COG, n = 25), with no exercise instructions. All participants were taking oral antidiabetic drugs, and none had diabetic complications. Clinical parameters, exercise capacity (VO_2peak), ventilatory threshold (VT), insulinresistance indices (fasting insulin, HOMA-IR, HOMA%S), hsCRP, fibrinogen, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed at baseline and after 16 weeks.ResultsNo significant changes were found in body mass index, waist/hip ratio, insulin-resistance indices, MMP-2 and TIMP-1 throughout the study in either group (P > 0.05). Compared with controls, the EXG showed a significant decrease in systolic and mean blood pressure, total and LDL cholesterol, and HbA_1c (P < 0.05). Also, exercise significantly suppressed levels of fibrinogen (P = 0.047), hsCRP (P = 0.041) and MMP-9 (P = 0.028), and the MMP-9-to-TIMP-1 ratio (P = 0.038), whereas VO_2peak (P = 0.011), VT (P = 0.008) and plasma TIMP-2 levels (P = 0.022) were considerably upregulated in the EXG vs. COG. Standard multiple-regression analyses revealed that MMP-9 changes were independently associated with fibrinogen and HbA_1c changes, while fibrinogen changes independently predicted TIMP-2 alterations with exercise.ConclusionMostly self-controlled exercise of moderate intensity ameliorated serum levels of pro- and anti-atherogenic markers in patients with T2DM, with no effects on body weight. These data offer further insight into the cardioprotective mechanisms of exercise in patients with T2DM.     

Effects of a group-based exercise program on the physical performance,muscle strength and quality of life in older women

This study was aimed at determining the effect of a group-based exercise program on the physical performance, muscle strength and quality of life (QoL) in older women. Twenty women performed an exercise program for 8 weeks, at the rehabilitation unit. Outcome measures included a 4-m and 20-m walk test, a 6-min walk test, stair climbing and chair rise time, timed up and go test, isokinetic muscle testing of the knee and ankle, and the short form-36 (SF-36) and geriatric depression scale (GDS) questionnaires. The mean age of the study group was 70.3 ± 6.5 years. After the completion of the exercise program, all of the physical performance tests and the SF-36 scores for the participants showed statistically significant improvements (p < 0.05). In the isokinetic evaluations, most of angular velocities showed a significant increase in the peak torque (PT) values for knee extension and flexion, and for ankle plantar flexion (p < 0.05). We concluded that this exercise program, when applied to older women, resulted in improved physical performance, increased muscle strength measured in both the knee and ankle, and improvement in the scores, estimating the QoL. We have shown that this exercise program is both effective and reliable for this age group of women.     

Supervised home-based exercise may attenuate the decline of glucose tolerance in obese pregnant women

AimThe significant deterioration of insulin sensitivity and glucose tolerance during pregnancy can have serious health implications for both the pregnant woman and her baby. Although it is well established that regular exercise benefits insulin sensitivity in the nonpregnant population, the effect on glucose tolerance in obese pregnant women is not known. The purpose of this study was to investigate the effect of a supervised 10-week, home-based, exercise programme, beginning at week 18 of gestation, on glucose tolerance and aerobic fitness in previously sedentary obese women.MethodsTwelve sedentary obese women were randomized into an exercise (EX; n = 6) or control (CON; n = 6) group at 18 weeks of gestation. Those randomized to EX engaged in 10 weeks of supervised home-based exercise (three sessions a week of stationary cycling), while those in the CON group maintained their usual daily activity. Their glucose and insulin responses to an oral glucose tolerance test (OGTT), as well as their aerobic fitness, were assessed both pre- and postintervention.ResultsReduced glucose tolerance in the CON, but not EX, group was indicated by a tendency postintervention towards higher blood glucose levels at 1 h of the OGTT (P = 0.072). Furthermore, at 2 h of the postintervention OGTT, blood glucose tended to remain elevated from baseline in the CON (P = 0.077). There was also a trend towards increased fitness in the EX (P = 0.064), but not the CON group.ConclusionRegular aerobic exercise begun during pregnancy may have favourable effects on glucose tolerance and fitness in obese women, and warrants further investigation in a larger sample population.     

HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise

ObjectiveTo investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions.Materials/MethodsMice were divided into four groups (n = 10/group): 1) ALT = ad libitum + trained (1 h/d for 3 d/wk); 2) ALTH = ALT + HMB (0.5 g/kg BW/d); 3) C = calorie restricted (? 30%) + trained (6 h/d, 6 d/wk); and 4) CH = C + HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p < 0.05.ResultsALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes.ConclusionHMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions.     

Association of nutrition and immune-endocrine dysfunction with muscle mass and performance in cognitively impaired older adults

BackgroundWith lean mass declining early in Alzheimer’s disease, muscle quality beyond quantity is relevant to physical performance. We sought to identify potentially modifiable factors for the differential loss of muscle mass (pre-sarcopenia) and its performance (sarcopenia) in older adults with mild cognitive impairment (MCI) and mild-to-moderate Alzheimer’s disease (AD).MethodsThis is a cross-sectional study of 108 community-dwelling older adults with MCI and mild-to-moderate AD. Participants were categorized as: (i) No sarcopenia (normal muscle mass), (ii) Pre-sarcopenia (low muscle mass without weakness or slowness), (iii) Sarcopenia (low muscle mass AND weak grip strength and/or slow gait speed) using Asian cut-offs. Muscle quality was defined as the ratio of grip and knee extension strength to average arm and leg lean mass respectively. We measured cognitive, functional and physical (Short Physical Performance Battery, SPPB) performance; physical activity level; nutritional status; and blood biomarkers of inflammation and endocrine dysfunction.ResultsSPPB (p = 0.033) and activity level (p = 0.010) were highest in the pre-sarcopenic group. Pre-sarcopenic group had highest arm muscle quality [10.6 (7.7–12.2) vs 13.9 (12.6–15.7) vs 11.3 (9.7–12.8), p < 0.001], despite significantly lower appendicular lean mass than non-sarcopenic group. In multi-nomial logistic regression reference to non-sarcopenic group, malnutrition independently increased risk for both pre-sarcopenia (Relative risk = 7.53, 95% C.I 1.20–47.51, p = 0.032) and sarcopenia (Relative risk = 11.91, 95% C.I 2.85–49.77, p = 0.001). A combined pro-inflammatory and endocrine deficient state significantly increased the risk of sarcopenia (Relative risk = 5.17, 95% C.I 1.31–20.37, p = 0.019).ConclusionMalnutrition is a precursor for progressive loss of muscle mass, but a pro-inflammatory and endocrine deficient state may potentially aggravate decline in muscle quality to culminate in frank sarcopenia.     

Irisin and leptin concentrations in relation to obesity,and developing type 2 diabetes: A cross sectional and a prospective case-control study nested in the Normative Aging Study

ObjectiveTo investigate the associations between irisin and leptin levels in obesity and insulin resistance in a cross sectional study. To assess the potential role of irisin and leptin as a predictive marker of T2DM using a nested case-control study.MethodsBoth studies were designed within the longitudinal VA NAS cohort. The cross sectional study involved 111 non obese and 105 obese subjects who were subdivided into two groups based on their fasting glucose tolerance. In the nested 1:3 case-control study, 47 subjects with T2DM and 140 non-diabetic controls were selected. Serum samples collected 3-5 years before the diagnosis of T2DM were analyzed. Irisin and leptin concentrations were measured using a validated ELISA and radioimmunoassay respectively.ResultsIn the cross-sectional study, irisin did not differ between groups based on their fasting glucose tolerance. When subjects were grouped based on obesity status, both irisin and leptin concentrations were significantly higher in obese compared to the non-obese group (p = 0.03 and < 0.001, respectively). Irisin concentrations positively correlated with leptin concentrations (r = 0.392, P < 0.001). In the nested case control study, leptin concentrations were a significant predictor of developing diabetes (p = 0.005) in unadjusted models, but not after correcting for BMI, whereas irisin concentrations did not play a role of comparable significance.ConclusionsLeptin concentrations are higher in the obese group irrespective of their glucose tolerance. Obese individuals with impaired fasting glucose have higher concentrations of circulating irisin compared to non-obese subjects with normal glucose tolerance. Irisin concentrations do not predict risk of developing diabetes prospectively.     

Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men

ObjectivesLow-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH–) a family history of type 2 diabetes.MethodsFollowing a 3-day lead in energy balanced diet, FH+ (n = 9) and FH– men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11).ResultsBody weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P < 0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04).ConclusionOverfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.     

Evaluation of serum zonulin level in prediabetic patients

BackgroundThis study aimed to investigate the relationship between lipopolysaccharide (LPS) and zonulin levels and also to show the effect of acute hyperglycemic stress induced by oral glucose tolerance testing (OGTT) on zonulin levels in pre-diabetic patients.MethodsFour groups were constituted according to the criteria of the American Diabetes Association (ADA), based on OGTT results: control group (n:40); prediabetic group (n:56), divided into two subgroups: impaired fasting glucose group (IFG) (n:36), and impaired glucose tolerance (IGT) + IFG group (n:20) and type-2 diabetes mellitus (T2DM) group (n:45).ResultsZonulin and LPS did not significantly differ between the prediabetes and control groups, but were significantly higher in the T2DM group compared to both the prediabetic and the control group (P < 0.001). After OGTT, zonulin and LPS were significantly higher in the prediabetes group compared to the control group (P < 0.01 and P < 0.05, respectively), and significantly lower in the IFG and IFG + IGT groups compared to the T2DM group (P < 0.001, P < 0.001 and P < 0.001, P < 0.001, respectively). A positive correlation was detected between fasting zonulin and 2-hour zonulin (r = 0.727, P < 0.001) and between fasting LPS (r = 0.555, P < 0.001) and 2-hour LPS (r = 0.567, P < 0.001) in the prediabetic group. Increased zonulin and LPS levels and the positive correlation between these levels during the prediabetic period although non significant suggests onset of intestinal permeability.ConclusionsDuring acute hyperglycemia in prediabetic patients, up-regulation of zonulin and LPS may affect intestinal function. The intestines may play a key role in up-regulation of glucose and the pathogenesis of diabetes.     

Measurement of muscle insulin sensitivity in obese men

AimsIn 2007, a novel estimate of skeletal muscle insulin sensitivity was derived from the oral glucose tolerance test (OGTT). The aim of this investigation is to assess whether and to what extent the proposed index of skeletal muscle insulin sensitivity derived from the OGTT was associated with muscle insulin sensitivity measured using the hyperinsulinemic-euglycaemic clamp technique.MethodsForty-six middle-aged, abdominally obese men (age 44 ± 8 years, waist circumference 107.4 ± 6.2) were studied. Each participant participated in a 2-hour, 75-g OGTT and a 3-hour hyperinsulinemic-euglycaemic clamp protocol.ResultsThe OGTT-derived index of muscle insulin sensitivity correlated with muscle insulin sensitivity measured with the insulin clamp (r = 0.55, P < 0.01), however, the standard error of estimate (SEE) when predicting muscle insulin sensitivity by the OGTT-derived index was 5.3 (50%).ConclusionOur findings suggest that despite a statistically significant association between the two methods, the OGTT approach lacks precision and is not a useful method for estimating skeletal muscle insulin sensitivity in abdominally obese men.