Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease

Background and Objective High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease. Patients and Measurements We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54·4 ± 1·8 years) or HD (n = 38, 22 males and 16 females, age 60·8 ± 1·6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history. Results PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28·7 (13·0–71·9) µg/l] than those found in patients on HD [9·7 (4·7–31·9) µg/l, P < 0·01] or in conservative management [5·9 (4·3–38·6) µg/l, P < 0·05]. Adiponectin concentrations were similar in the three groups of patients (mean ± SEM, 48·0 ± 4·5 mg/l in PD, 57·7 ± 4·4 mg/l in HD, and 44·4 ± 7·0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26·3 ± 0·99 and 27·5 ± 1·4 µg/l, respectively, vs. 17·3 ± 1·0 µg/l, P < 0·001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0·287, P < 0·01) and adiponectin levels were negatively related to BMI (r = ?0·416, P < 0·001) and the homeostatic model assessment (HOMA‐R) index (r =?0·216, P < 0·05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1·80 (1·03–3·15), P = 0·039] was found when analysing subgroups of patients. Conclusions These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.     

The ratio of glycated albumin to glycated haemoglobin correlates with insulin secretory function

Objective Although glycated haemoglobin (A1c) levels are similar among patients with type 2 diabetes, the glycated albumin (GA)/A1c ratio varies considerably. On the basis of the hypothesis that endogenous insulin secretion might be correlated with the GA/A1c ratio, we investigated whether insulin secretory function or insulin resistance has different effects on the GA/A1c ratio in patients with type 2 diabetes using the standardized liquid meal test. Design A clinical, retrospective study. Patients and measurements A total of 758 patients with type 2 diabetes ingested a standardized liquid meal (i.e. 500 kcal, 17·5 g fat, 68·5 g carbohydrate and 17·5 g protein). The subjects were divided into two groups: those with GA/A1c ratio <2·5 (n = 414) and those with GA/A1c ratio ≥2·5 (n = 344). We compared the A1c and GA levels, and the GA/A1c ratio and evaluated the relationships between the glycaemic indices and other parameters. Effects of β‐cell function [homeostasis model assessment (HOMA‐β), insulinogenic index (IGI)] and insulin resistance (HOMA‐IR) on the GA/A1c ratio were also examined. Results The GA/A1c ratio was significantly correlated with HOMA‐β, IGI and body mass index (BMI) but not with HOMA‐IR. Furthermore, after adjusting for age, gender, BMI, haemoglobin and albumin levels, the GA/A1c ratio was still inversely correlated with both HOMA‐β and IGI. Conclusions The GA/A1c ratio is significantly correlated with insulin secretory function but not with insulin resistance.     

Comparison of annual variability in HbA1c and glycated albumin in patients with type 1 vs. type 2 diabetes mellitus

ObjectiveIt has been suggested that plasma glucose (PG) levels per se and long-term variations in PG levels are associated with diabetic vascular complications. Glycated albumin (GA) reflects shorter-term glycemic control, as well as postprandial PG levels, as compared to HbA1c. In this study, we hypothesized that GA more strongly reflects long-term variations in PG levels than HbA1c, and compared the variability of HbA1c and that of GA in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).MethodsThis study included 8 T1DM patients and 48 T2DM patients. Over a 1-year period, HbA1c and GA were measured every month and the mean values and coefficients of variation (CV) for each patient were calculated.ResultsIn both T1DM and T2DM patients, the CV of GA was significantly higher than the CV of HbA1c. Both the CV of HbA1c and the CV of GA were significantly higher in the T1DM patients than in the T2DM patients.ConclusionThe annual variability in GA was greater than that in HbA1c. In addition, the annual variability in HbA1c and that in GA in the T1DM patients were greater than in the T2DM patients. Our findings suggest that GA more accurately reflects long-term variations in PG levels than HbA1c.     

Association of glycated albumin, but not glycated hemoglobin, with calcaneus quantitative ultrasound in male hemodialysis patients with type 2 diabetes mellitus

Sustained high glucose impairs bone metabolism in patients with type 2 diabetes mellitus (T2DM). In this study, the relationship between glycemic control and bone metabolism was examined in male hemodialysis (HD) patients with T2DM. To avoid the effect of menstruation and the menstrual cycle, obesity, and glycosuria-induced hypercalciuria on bone metabolism, male anuric nonobese HD patients with T2DM (n = 42) were enrolled. Calcaneus stiffness index (SI) was determined using ultrasound after HD session. Casual plasma glucose (PG), glycated hemoglobin (HbA_1c), and glycated albumin (GA) were measured before the HD session. In simple regression analysis, log PG (r = −0.333, P < .05) and log GA (r = −0.350, P < .05), but not log HbA_1c (r = −0.134, P = .3985), exhibited significant and negative correlations with calcaneus SI. In multiple regression analysis including log BMI, log cCa × Pi product, and log PG, log PG was associated significantly in a negative manner with calcaneus SI, in addition to log cCa × Pi product. When log PG was replaced with log GA or log HbA_1c, log GA, but not log HbA_1c, emerged as a significant factor associated. The mechanism as to why HbA_1c failed to associate could be explained by its false reduction by erythropoietin injection. The present study supported the notion of GA as an appropriate indicator for glycemic control in HD patients with T2DM. Furthermore, it is suggested that poor glycemic control might be a significant factor toward decreasing calcaneus SI in T2DM HD patients.     

Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency

objective To investigate the role of IGF‐1 on intima–media thickness (IMT) at common carotid arteries by Doppler ultrasonography. subjects Thirty‐nine patients (17 women, 22 men, aged 25–70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF‐1 levels, and 39 sex‐, age‐ and body mass index (BMI)‐matched healthy controls. results Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0·88 ± 0·26 vs. 0·69 ± 0·14 mm, P < 0·001), and systolic and diastolic peak velocity (P < 0·001) compared to controls. Eight patients (18%) and one control (2·1%, P = 0·04) had well‐defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0·78, P < 0·001). In both controls (r = ?0·82; P < 0·0001) and patients with GHD (r = ?0·84, P < 0·0001), serum IGF‐1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH‐deficient patients were total cholesterol levels (t = 5·2, P < 0·001), followed by disease duration (t = 2·4, P = 0·02), while in controls the variables most significantly related to IMT were IGF‐1 levels (t = ?9·9, P < 0·001), followed by low density lipoprotein (LDL)‐cholesterol levels (t = ?2·3, P = 0·02). Compared to patients with normal IGF‐1 levels, those with low IGF‐1 levels had lower high density lipoprotein (HDL)‐cholesterol levels (1·0 ± 0·2 vs. 1·3 ± 0·2 mmol/l, P = 0·0002), and higher glucose (54·3 ± 6·1 vs. 48·9 ± 5·9 mmol/l, P = 0·008), insulin (25·2 ± 6·8 vs. 18·8 ± 6·0 mUl/l, P = 0·004), total cholesterol (7·1 ± 1·1 vs. 4·9 ± 0·6 mmol/l, P < 0·0001), total/HDL‐cholesterol ratio (7·2 ± 1·8 vs. 3·9 ± 0·7, P < 0·0001), fibrinogen levels (319·8 ± 56·9 vs. 241·8 ± 53·0 mg/dl, P < 0·0001) and mean IMT at common carotid arteries (1·05 ± 0·25 vs. 0·69 ± 0·07 mm, P < 0·0001). Atherosclerotic plaques were found only in GH‐deficient patients with low IGF‐1 levels. conclusions GH‐deficient patients have alterations in lipid profile with an increase in the total/HDL‐cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF‐1 deficiency have increased IMT.     

Amelioration of cardiovascular risk factors with partial biochemical control of acromegaly

Objective Complete remission of acromegaly is associated with favourable changes in cardiovascular risk parameters. We evaluated the effects of suboptimal therapy on haemodynamic, metabolic, inflammatory and coagulation cardiovascular risk indices. Design and methods Eighteen acromegalic patients on somatostatin analogues, with incomplete biochemical control, were evaluated at diagnosis and 6 months after treatment and compared to 15 healthy age‐ and body mass index (BMI)‐matched controls. Measurements of blood pressure, GH, IGF‐I, glucose, insulin, glycated haemoglobin (HbA1c), lipids, apolipoprotein A1 (apoA1), apoB, high‐sensitivity C‐reactive protein (hs‐CRP), fibrinogen, plasminogen activator inhibitor 1 (PAI‐1), tissue plasminogen activator (tPA) and circulating thrombomodulin were performed in all study participants, followed by an oral glucose tolerance test (OGTT). Insulin sensitivity (IS) was expressed by the Matsuda index (OGTT_ISI). Results Partial control of acromegaly resulted in a significant reduction in systolic and diastolic blood pressure, glucose, insulin, HbA1c, total (T‐C) and low density lipoprotein cholesterol (LDL‐C) and triglyceride levels, and a significant increase in apoA1, high density lipoprotein cholesterol (HDL‐C) and OGTT_ISI compared to pretreatment levels. Plasma fibrinogen and PAI‐1 levels fell significantly [respectively (mean ± SEM), 11·04 ± 0·41 vs. 10·12 ± 0·34 µmol/l, P = 0·003 and 9·6 ± 1·97 vs. 6·55 ± 1·89 µg/l, P < 0·001]. However, a marked reduction in tPA [median (IQR) 5·1 (2·5–15) vs. 3·4 (2·4–8·6) µg/l, P = 0·031] and an increase in hs‐CRP [median (IQR) 0·05 (0·03–0·11) vs. 0·1 (0·06–0·23) mg/l, P < 0·001] were also noted. On treatment, acromegalic patients were comparable to controls, except for OGTT_ISI, lipoprotein(a) [Lp(a)], fibrinogen and tPA and HDL‐C levels. Thrombomodulin and apoB levels were not affected by treatment. Conclusions Partial control in disease activity following somatostatin analogues results in significant improvement in a considerable number of cardiovascular risk markers in acromegaly.     

Association of time in range with hemoglobin A1c,glycated albumin and 1,5-anhydro-d-glucitol

Aims/IntroductionHemoglobin A1c (HbA1c), glycated albumin (GA) and 1,5‐anhydro‐d‐glucitol (1,5‐AG) are used as indicators of glycemic control, whereas continuous glucose monitoring (CGM) is used to assess daily glucose profiles. The aim of this study was to investigate the relationships between CGM metrics, such as time in range (TIR), and glycemic control indicators.Materials and MethodsWe carried out retrospective CGM and blood tests on 189 outpatients with impaired glucose tolerance (n = 22), type 1 diabetes mellitus (n = 67) or type 2 diabetes mellitus (n = 100).ResultsIn type 1 diabetes mellitus and type 2 diabetes mellitus patients, HbA1c and GA were negatively correlated with TIR, whereas 1,5‐AG was positively correlated with TIR. In type 1 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5‐AG of 6.9% (95% confidence interval [CI] 6.5–7.2%), 20.3% (95% CI 19.0–21.7%) and 6.0 µg/mL (95% CI 5.1–6.9 µg/mL), respectively. In type 2 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5‐AG of 7.1% (95% CI 7.0–7.3%), 19.3% (95% CI 18.7–19.9%) and 10.0 µg/mL (95% CI 9.0–11.0 µg/mL), respectively. TIR values corresponding to HbA1c levels of 7.0% were 56.1% (95% CI 52.3–59.8%) and 74.2% (95% CI 71.3–77.2%) in type 1 diabetes mellitus and type 2 diabetes mellitus patients, respectively.ConclusionsThe results of this study showed that the estimated HbA1c corresponding to a TIR of 70% was approximately 7.0% for both type 1 diabetes mellitus and type 2 diabetes mellitus patients, and that the estimated 1,5‐AG calculated from the TIR of 70% might be different between type 1 diabetes mellitus and type 2 diabetes mellitus patients.     

Serum resistin is positively correlated with the accumulation of metabolic syndrome factors in type 2 diabetes

Objective Resistin, secreted from adipocytes, causes insulin resistance in rodents. We reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at ?420 increases type 2 diabetes (T2DM) susceptibility by enhancing promoter activity. We also showed that serum resistin was positively correlated with G at SNP‐420, the duration of T2DM, and HbA1c in T2DM. The aim of this study was to determine the relation between serum resistin and factors related to the metabolic syndrome (MetS) in T2DM. Design, patients and measurements We analysed 238 Japanese T2DM subjects (124 males and 114 females, age 60·2 ± 11·3 years, body mass index (BMI) 24·1 ± 3·9) whose overnight fasting sera were available. Serum resistin was measured using ELISA. Results Serum resistin was higher in subjects with either obesity (P = 0·041), low HDL (P = 0·004), high triglycerides (TG) (P = 0·019), hypertension (HT) (P = 0·001) or atherosclerosis (P = 0·012). Simple regression analysis revealed that serum resistin was correlated with lower HDL, TG and high‐sensitivity C‐reactive protein (hsCRP). Multiple regression analysis (or logistic regression analysis for HT), adjusted for age, gender, BMI and the duration of T2DM, revealed that serum resistin was correlated with lower HDL (P = 0·008), TG (P = 0·041), HT (P = 0·031) and hsCRP (P = 0·004). Serum resistin was positively correlated with the number of MetS factors, independent of age, gender and the duration of T2DM (P < 0·001). Adjustment by either thiazolidinedione (TZD) treatment or hsCRP had no effects on these findings. Conclusions Serum resistin was positively correlated with the accumulation of MetS factors in T2DM.     

Correlation of the hypotonic shock response and extent of shape change with the new ThromboLUX™

ThromboLUX (TLX)‐Score was compared with hypotonic shock response (HSR) and extent of shape change (ESC) in 99 samples from 42 platelet concentrates. Tests were performed in parallel and duplicate. Mean values for TLX Score, HSR and ESC were 30·3 ± 3·8%, 69·0 ± 12·2% and 23·2 ± 4·9%, respectively. We found no significant correlation between TLX Score and HSR or ESC (r = ?0·158, P = 0·118 and r = ?115, P = 0·255, respectively), whereas HSR and ESC correlated significantly (r = 0·351, P < 0·001). As TLX Score did not show significant correlation with HSR and ESC, the value of TLX for platelet quality testing remains unclear. Studies comparing these parameters with transfusion outcome are needed.     

Left ventricular dysfunction in Klinefelter syndrome is associated to insulin resistance, abdominal adiposity and hypogonadism

Objective Epidemiological data suggest there is an increased risk of dying from heart disease among patients with Klinefelter syndrome (KS). Due to high prevalence of hypogonadism and metabolic syndrome, we speculated that patients with KS may have subclinical changes in the left ventricular function. Therefore, the aim was to assess left ventricular long axis function by tissue Doppler echocardiography in patients with KS and relate these findings to the metabolic status and testosterone levels. Design Cross-sectional study. Out-patient clinic. Patients We investigated 25 unselected patients with KS, recruited from endocrine and fertility clinics. Twenty-five age-matched males served as controls. Measurements Left ventricular systolic long axis function (velocities and strain rate) assessed by tissue Doppler echocardiography related to free testosterone, fasting values of plasma glucose, insulin, homeostasis model assessment (HOMA)-index, cholesterol and triglycerides in addition to dual energy X-ray absorptiometry (DEXA) scan derived assessment of truncal body fat. Results The long axis function was significantly reduced in patients with KS (peak systolic velocities 4·4 ± 1·3 vs. 5·3 ± 1·0 cm/s, P < 0·01 and strain rate –1·3 ± 0·3 vs.–1·6 ± 0·3 s⁻¹, P < 0·01). However, the ventricular dysfunction was mainly attributed KS patients with metabolic syndrome. The peak systolic velocities were significantly correlated to truncal body fat (r = –0·72, P < 0·01) and free testosterone (r = 0·63, P < 0·01), but uncorrelated to plasma glucose, insulin and HOMA-index. Conclusion Systolic long axis function is decreased in patients with KS and metabolic syndrome. The decrease in myocardial systolic function was significantly related to truncal body fat and hypogonadism, but not correlated to insulin sensitivity.     

Glycaemic control and body mass index in late‐adolescents and young adults with Type 1 diabetes mellitus: a population‐based study

Aims Studies of children with diabetes up to the age of 15 years report deteriorating glycaemic control in the early teenage years. The aim was to investigate glycaemia and body mass index in older teenagers and young adults. Method A Scottish, regional, population‐based, cross‐sectional study of 255 young people (117 female, 138 male) with Type 1 diabetes, aged 15–25 years (mean ±sd 19.8 ± 2.8 years, diabetes duration: 8.8 ± 5.4 years) registered on a diabetes database. Glycaemic control, body mass index (BMI) and insulin regimens were assessed in three age groups [group 1 (n = 96) 15–18 years; group 2 (n = 74) 18.1–22 years; and group 3 (n = 85) 22.1–25 years]. Results Subjects in the oldest age group had a significantly lower mean HbA_1c than those in the youngest age group (8.8 ± 1.7 vs. 9.9 ± 1.9%; P < 0.001). Mean BMI was higher in group 3 (25.2 ± 3.4 kg/m²) compared with group 1 (23.9 ± 3.1 kg/m²; P < 0.001). HbA_1c levels were higher in the younger subjects and women. Lower HbA_1c levels were associated with a higher BMI (r = ?0.324, P < 0.001) in men only. Overall, 74% took three or more injections a day, of whom 60% were on basal/bolus therapy. The proportion on basal/bolus insulin therapy increased with age and duration of diabetes. Conclusion Compared with adolescents, young adults with Type 1 diabetes have better glycaemic control and higher BMI. This was associated with lower insulin requirements.     

ORIGINAL ARTICLE: Pioglitazone improvement of fasting and postprandial hyperglycaemia in Mexican‐American patients with Type 2 diabetes: a double tracer OGTT study

Objectives By using tracer techniques, we explored the metabolic mechanisms by which pioglitazone treatment for 16 weeks improves oral glucose tolerance in patients with type 2 diabetes when compared to subjects without diabetes. Methods In all subjects, before and after treatment, we measured rates of tissue glucose clearance (MCR), oral glucose appearance (RaO) and endogenous glucose production (EGP) during a (4‐h) double tracer oral glucose tolerance test (OGTT) (1‐¹⁴C‐glucose orally and 3‐³H‐glucose intravenously). Basal hepatic insulin resistance index (HepIR) was calculated as EGPxFPI. β‐cell function was assessed as the incremental ratio of insulin to glucose (ΔI/ΔG) during the OGTT. Results Pioglitazone decreased fasting plasma glucose concentration (10·5 ± 0·7 to 7·8 ± 0·6 mm , P < 0·0003) and HbA1c (9·7 ± 0·7 to 7·5 ± 0·5%, P < 0·003) despite increased body weight and no change in plasma insulin concentrations. This was determined by a decrease both in fasting EGP (20·0 ± 1·1 to 17·3 ± 0·8 μmol/kg_ffm min, P < 0·005) and HepIR (from 8194 declined by 49% to 3989, P < 0·002). During the OGTT, total glucose Ra during the 0‐ to 120‐min time period following glucose ingestion decreased significantly because of a reduction in EGP. During the 0‐ to 240‐min time period, pioglitazone caused only a modest increase in MCR (P < 0·07) but markedly increased ΔI/ΔG (P = 0·003). The decrease in 2h‐postprandial hyperglycaemia correlated closely with the increase in ΔI/ΔG (r = ?0·76, P = 0·004) and tissue clearance (r = ?0·74, P = 0·006) and with the decrease in HepIR (r = 0·62, P = 0·006). Conclusions In diabetic subjects with poor glycaemic control, pioglitazone improves oral glucose tolerance mainly by enhancing the suppression of EGP and improving β‐cell function.     

Abnormal heart rate recovery after maximal cardiopulmonary exercise stress testing in young overweight women with polycystic ovary syndrome

Objective Heart rate recovery (HRR) is a measure derived from exercise test, defined as the fall in heart rate during the first minute after maximal exercise. Abnormal HRR is a measure of autonomic dysfunction associated with an increased mortality. This study was performed to evaluate the HRR in polycystic ovary syndrome (PCOS). Design Prospective controlled clinical study. Patients Seventy‐five PCOS women compared to 75 healthy women matched for age (21·7 ± 2·1 years vs. 21·9 ± 1·8 years, respectively) and body mass index (BMI) (29·0 ± 2·6 kg/m² vs. 29·1 ± 2·9 kg/m², respectively). Measurements Subjects were studied for their hormonal and metabolic profile, and underwent cardiopulmonary exercise test (CPX). Results PCOS women showed a significantly reduced HRR (12·9 ± 1·8 vs. 20·4 ± 3·1 beats/min, P < 0·001) compared to healthy controls, an impairment in maximal oxygen consumption (18·0 ± 2·3 ml/kg/min vs. 29·3 ± 3·9 ml/kg/min) and in oxygen consumption at anaerobic threshold (13·6 ± 2·6 ml/kg/min vs. 24·2 ± 3·0 ml/kg/min). In PCOS women, abnormal HRR was inversely correlated to BMI (r = ?0·582, P < 0·001) and to the area under the curve for insulin (r = ?0·596, P < 0·001). Conclusions Our data demonstrate an abnormal HRR after maximal CPX in young overweight PCOS patients, and that HRR should be investigated as a further potential marker of increased cardiovascular risk in PCOS.     

Inflammatory markers and visceral fat are inversely associated with maximal oxygen consumption in women with polycystic ovary syndrome (PCOS)

Background We investigated whether several different inflammatory markers including C‐reactive protein (CRP) and fibrinogen and white blood cells (WBCs) count, are associated with maximal oxygen consumption (VO_2max) in women with polycystic ovary syndrome (PCOS). Methods In PCOS women (n = 124, 24·1 ± 4·5 year‐old) VO_2max was measured during symptom‐limited cardiopulmonary exercise test. Abdominal fat distribution was determined by ultrasound. Physical activity level was assessed by a standardized questionnaire. CRP was measured by immunoassays, fibrinogen by the Clauss method, and WBCs count with a Coulter counter. Results Pearson's analysis showed a significant correlation between VO_2max and logCRP (r = –0·437, P < 0·001), fibrinogen (r = –0·479, P < 0·001), and WBCs count (r = –0·438, P < 0·001). Multivariable logistic regression model showed that age (β = –0·127, P = 0·005), AUC_INS (β = –0·335, P < 0·001), HDL‐C (β = 0·390, P < 0·001), physical activity score (β = 0·238, P = 0·002), visceral fat (β =–0·184), P = 0·023), FAI (β = –0·291, P = 0·028); CRP (β = –0·216, P = 0·011), fibrinogen (β = –0·113, P = 0·008) and WBCs count (β = –0·177, P < 0·001) were significantly associated with VO_2max. Conclusions Acute‐phase reactants, such as CRP and fibrinogen, and WBCs count were independently and inversely associated with a direct measure of cardiorespiratory fitness (VO_2max) in women with PCOS, even after adjustment for physical activity level and other potential confounding factors. These findings add to the growing body of evidence linking inflammation to cardiorespiratory fitness in PCOS women.     

Age of diabetes diagnosis and diabetes duration associate with glycated haemoglobin

An earlier age of diagnosis (r = −0.28, p < 0.0001) and longer duration of type 2 diabetes (r = 0.26, p < 0.0001) were each found to correlate with higher HbA1c level, on analysis of a diabetes centre database in people under regular shared care. When combined, these biological variables strongly associate with the current HbA1c level.     

Adiponectin, skeletal muscle adiponectin receptor expression and insulin resistance following dexamethasone

Objective Skeletal muscle is a major site of adiponectin action and of glucocorticoid‐induced insulin resistance. Little human data exist however, regarding the impact of exogenous glucocorticoids on adiponectin receptors in skeletal muscle. Design and patients Twelve subjects with type 2 diabetes and 12 controls underwent blood sampling and muscle biopsy of vastus lateralis before and after 4 days of 4 mg dexamethasone. Measurements (i) Total and high molecular weight (HMW) plasma adiponectin, glucose and insulin; (ii) Skeletal muscle adiponectin receptor AdipoR1 and AdipoR2 mRNA levels by quantitative real time RT‐PCR. Results Baseline total adiponectin (8·0 ± 0·89 vs. 12·5 ± 1·46 µg/ml, P = 0·013), HMW adiponectin (2·8 ± 0·44 vs. 5·9 ± 1·04 µg/ml, P = 0·014) and AdipoR2 mRNA levels (mean ΔC_T 14·71 ± 0·35 vs. 13·37 ± 0·28, P = 0·017) were significantly lower in diabetic subjects. After dexamethasone, AdipoR2 mRNA fell in the controls but there was no change in the diabetic group, while there was a significant increase in total (P = 0·002) and HMW adiponectin (P < 0·001) across both groups. Total and HMW plasma adiponectin correlated with clinical and biochemical measures of insulin sensitivity. However following dexamethasone which increased insulin resistance, the relationship between adiponectin and the biochemical measures was lost. Conclusions Plasma adiponectin and skeletal muscle AdipoR2 mRNA expression are reduced in subjects with diabetes; both are likely to contribute to the observed insulin resistance. Dexamethasone inhibits AdipoR2 mRNA expression in nondiabetic subjects, while there is a small rise in plasma adiponectin levels. The close relationship between plasma adiponectin and biochemical measures of insulin sensitivity is lost in the setting of glucocorticoid‐induced insulin resistance.     

Total, free and bound leptin and thyroid function in elderly women with different body weights

Objective The present study was aimed at evaluating the relationship of total leptin, and its free leptin (FL) and bound leptin (BL) fractions with adipose mass in very old euthyroid women, in relationship to thyroid function. Subjects and methods Twenty‐five older women (age: 73–95 years) were studied. Subjects representing underweight, normal weight and overweight/obese conditions were included. Plasma leptin, TSH, free T₄ (FT₄) and free T₃, (FT₃) total and HDL cholesterol were measured. FL and BL were evaluated by Fast Protein Liquid Chromatography (FPLC) analysis. Results Plasma leptin concentration was positively correlated with body mass index (BMI) (r = 0·64, P = 0·0005) and tricipital skin‐fold thickness (TF) (r = 0·46, P = 0·0187). Leptin was positively correlated with TSH (r = 0·50, P = 0·0116) and inversely with FT₃ (r = –0·40, P = 0·0477). TSH correlated with the adiposity indexes BMI (r = 0·40, P = 0·05) and TF (r = 0·42, P = 0·0336). Plasma FT₃ was positively correlated with FT₄ (r = 0·49, P = 0·012). FL and BL were evaluated in 8 out of 25 subjects. FL positively correlated with BMI (r = 0·81, P = 0·0218) and leptin (r = 0·83, P = 0·0004), whereas BL did not correlate with these parameters. Conclusions The present results indicate that in very old women, plasma leptin concentrations reflect the extent of adipose mass and suggest that a complex regulatory interaction exists between leptin and thyroid function, possibly taking place at central (hypothalamus–pituitary) and peripheral (deiodinase activity) levels.     

Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study

Objective We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug‐naïve type 2 diabetic patients. Design, Patients, and Measurements In this 52‐week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0–10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C‐peptide, and glucagon levels, homoeostasis model assessment‐insulin resistance (HOMA‐IR) and β‐cell function (HOMA‐B), insulinogenic index (IGI, defined as 30–0 min insulin/30–0 min glucose), and area under the curve for glucose, insulin, and C‐peptide obtained after 75‐g oral glucose tolerance test. Results After 52 weeks, mean HbA1c levels and fasting and postload 2‐h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm , and 17·5 ± 5·1 to 10·9 ± 3·6 mm , respectively (P < 0·01). HOMA‐B and IGI increased significantly from 50·3 ± 33·5 to 75·1 ± 32·8 and from 11·3 ± 1·3 to 35·0 ± 6·3 at 52 weeks, respectively (P < 0·01). Multivariate regression analysis indicated that the reduction in HbA1c was significantly associated with high baseline HbA1c, low IGI, and short duration of diabetes after adjusting for age, sex, body mass index, blood pressure, triglycerides, creatinine, high‐sensitivity CRP, glucagon, C‐peptide, HOMA‐B, and HOMA‐IR. No severe adverse events were observed. Conclusion These results suggest that drug‐naïve type 2 diabetic patients with low β‐cell function would benefit the most from early initial combination therapy of sitagliptin and metformin.     

Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy

Objective Adiponectin is secreted specifically from adipocytes, and improves insulin sensitivity. Of its isoforms, the high molecular weight (HMW) complex is thought to be the most active. The aim of this study was to determine the relationship between serum total or HMW adiponectin and diabetic microangiopathy. Design, patients and measurements We analysed 198 Japanese patients with type 2 diabetes mellitus (T2DM) whose fasting serum samples were available. Serum total adiponectin and HMW adiponectin were measured using an enzyme‐linked immunosorbent assay (ELISA). Results Serum total adiponectin was found to have increased in the advanced stages of diabetic retinopathy (mean ± SE, none, 6·9 ± 0·3; simple, 8·3 ± 1·0; preproliferative, 8·4 ± 0·8; proliferative, 12 ± 1·1 mg/l; anova P = 0·0004) and nephropathy (stage I, 7·0 ± 0·3; II, 7·7 ± 0·5; III, 9·5 ± 0·9; IV, 16 ± 4·5 mg/l, P < 0·0001). Similarly, serum HMW adiponectin had increased in the advanced stages of retinopathy (3·7 ± 0·2, 4·6 ± 0·5, 4·6 ± 0·6 and 6·9 ± 0·8 mg/l, respectively, P = 0·0005) and nephropathy (3·7 ± 0·2, 4·3 ± 0·4, 5·3 ± 0·7 and 7·9 ± 2·2 mg/l, respectively, P = 0·0007). Neither serum total nor HMW adiponectin was correlated with neuropathy. The HMW/total adiponectin ratio was not correlated with microangiopathy. Multiple regression analysis revealed that serum total and HMW adiponectin were independent factors for retinopathy stage (P = 0·0055 and P = 0·0027, respectively) and nephropathy stage (P = 0·0003 and P = 0·0018, respectively), when adjusted for age, gender, body mass index (BMI) and the duration of T2DM. This correlation remained significant when serum creatinine (or estimated glomerular filtration rate) and hypertension were added as independent variables. Treatment with thiazolidinediones (TZDs) did not affect these findings. Conclusions Serum total adiponectin and HMW adiponectin were found to be positively correlated with the severity of retinopathy and nephropathy but not with neuropathy in T2DM.     

Intravenous zoledronate improves bone density in adults with cystic fibrosis (CF)

Objective Reduced bone mineral density (BMD) and increased rates of atraumatic fracture are observed in cystic fibrosis (CF) patients, causing increasing morbidity as this population ages. The study aimed to assess the safety, tolerability and effect on BMD of intravenous zoledronate in adults with CF and osteopaenia. Design Randomized, double‐blind, placebo‐controlled clinical trial. Setting Adult CF outpatient clinics at two hospitals. Patients Twenty‐two non‐transplanted CF patients aged ≥ 18 years with a bone densitometry T‐score of < –1·5 at one of three sites (lumbar spine, femoral neck, distal forearm) were studied. Participants were randomized to receive either 2 mg zoledronate IV (n = 10) or normal saline (placebo, n = 12) every 3 months for 2 years (8 infusions). All participants received calcium and vitamin D supplements twice daily. Measurements Percentage change in areal BMD from baseline. Results Lumbar spine BMD increased from baseline more with zoledronate than placebo at 6 months (5·35 ± 0·76 vs. 1·19 ± 1·20%, P = 0·012), 12 months (6·6 ± 1·5 vs. 0·35 ± 1·55%, P = 0·011) and 24 months (6·14 ± 1·86 vs. 0·44 ± 0·10, P = 0·021). Femoral neck BMD increased more after zoledronate than placebo at 6 months (3·2 ± 1·6 vs.–1·43 ± 0·43%, P = 0·019), 12 months (4·12 ± 1·8 vs.–1·59 ± 1·4%, P = 0·024) and 24 months (4·23 ± 1·3 vs.–2·5 ± 1·41%, P = 0·0028). Forearm BMD did not change. Zoledronate was associated with flu‐like and musculoskeletal side effects, particularly after the first infusion. There were no fractures in either group. Conclusion Intravenous zoledronate was significantly more effective than placebo for increasing BMD in adults with CF and osteopaenia, but side effects limited its tolerability.