Background:
While there are compelling observational data confirming that individuals who exercise are healthier, the efficacy of aerobic exercise interventions to reduce metabolic risk and improve insulin sensitivity in older people has not been fully elucidated. Furthermore, while low birth weight has been shown to predict adverse health outcomes later in life, its influence on the response to aerobic exercise is unknown. Our primary objective is to assess the efficacy of a fully supervised twelve week aerobic exercise intervention in reducing clustered metabolic risk in healthy older adults. A secondary objective is to determine the influence of low birth weight on the response to exercise in this group.Methods/DesignWe aim to recruit 100 participants born between 1931–1939, from the Hertfordshire Cohort Study and randomly assign them to no intervention or to 36 fully supervised one hour sessions on a cycle ergometer, over twelve weeks. Each participant will undergo detailed anthropometric and metabolic assessment pre- and post-intervention, including muscle biopsy, magnetic resonance imaging and spectroscopy, objective measurement of physical activity and sub-maximal fitness testing.DiscussionGiven the extensive phenotypic characterization, this study will provide valuable insights into the mechanisms underlying the beneficial effects of aerobic exercise as well as the efficacy, feasibility and safety of such interventions in this age group.Trial RegistrationCurrent Controlled Trials: ISRCTN60986572

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Background:
Most studies on cortisol have focused on smaller, selected samples. We therefore aimed to sex-specifically study the diurnal cortisol pattern and explore its association with abdominal obesity in a large unselected population.
Methods:
In 2001–2004, 1811 men and women (30–75 years) were randomly selected from the Vara population, south-western Sweden (81% participation rate). Of these, 1671 subjects with full information on basal morning and evening salivary cortisol and anthropometric measurements were included in this cross-sectional study. Differences between groups were examined by general linear model and by logistic and linear regression analyses.
Results:
Morning and ?-cortisol (morning – evening cortisol) were significantly higher in women than men. In both genders older age was significantly associated with higher levels of all cortisol measures, however, most consistently with evening cortisol. In women only, age-adjusted means of WHR were significantly lower in the highest compared to the lowest quartile of morning cortisol (p = 0.036) and ?-cortisol (p < 0.001), respectively. Furthermore, when comparing WHR above and below the mean, the age-adjusted OR in women for the lowest quartile of cortisol compared to the highest was 1.5 (1.0–2.2, p = 0.058) for morning cortisol and 1.9 (1.3–2.8) for ?-cortisol. All findings for ?-cortisol remained after adjustments for multiple covariates and were also seen in a linear regression analysis (p = 0.003).
Conclusion:
In summary, our findings of generally higher cortisol levels in women than men of all ages are novel and the stronger results seen for ?-cortisol as opposed to morning cortisol in the association with WHR emphasise the need of studying cortisol variation intra-individually. To our knowledge, the associations in this study have never before been investigated in such a large population sample of both men and women. Our results therefore offer important knowledge on the descriptive characteristics of cortisol in relation to age and gender, and on the impact that associations previously seen between cortisol and abdominal obesity in smaller, selected samples have on a population level.

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Background:
Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS(R)) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial.
Methods:
602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140-199 mg/dl). In addition, IGT subjects were required to have FPG = 95-125 mg/dl and at least one other high risk characteristics. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2-3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated.Primary endpoint is conversion of IGT to T2DM based upon FPG [greater than or equal to] 126 or 2-hour PG [greater than or equal to] 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance.
Conclusion:
ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM.Trial Registration: clinical trials.gov identifier: NCT00220961

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Background:
A lot of studies have showed an excess maternal transmission of type 2 diabetes (T2D). The aim, therefore, of the present study was to estimate the prevalence of familial history of T2D in Greek patients, and to evaluate its potential effect on the patient’s metabolic control and the presence of diabetic complications.
Methods:
A total of 1,473 T2D patients were recruited. Those with diabetic mothers, diabetic fathers, diabetic relatives other than parents and no known diabetic relatives, were considered separately.
Results:
The prevalence of diabetes in the mother, the father and relatives other than parents, was 27.7, 11.0 and 10.7%, respectively. Patients with paternal diabetes had a higher prevalence of hypertension (64.8 vs. 57.1%, P = 0.05) and lower LDL-cholesterol levels (115.12 ± 39.76 vs. 127.13 ± 46.53 mg/dl, P = 0.006) than patients with diabetes in the mother. Patients with familial diabetes were significantly younger (P < 0.001), with lower age at diabetes diagnosis (P < 0.001) than those without diabetic relatives. Patients with a diabetic parent had higher body mass index (BMI) (31.22 ± 5.87 vs. 30.67 ± 5.35 Kg/m2, P = 0.08), higher prevalence of dyslipidemia (49.8 vs. 44.6%, P = 0.06) and retinopathy (17.9 vs. 14.5%, P = 0.08) compared with patients with no diabetic relatives. No difference in the degree of metabolic control and the prevalence of chronic complications were observed.
Conclusion:
The present study showed an excess maternal transmission of T2D in a sample of Greek diabetic patients. However, no different influence was found between maternal and paternal diabetes on the clinical characteristics of diabetic patients except for LDL-cholesterol levels and presence of hypertension. The presence of a family history of diabetes resulted to an early onset of the disease to the offspring.

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