Elisabetta Dall'Aglio

Relationship between blood pressure and plasma insulin in non-obese and obese non-diabetic subjects

SummaryIn this study, we have measured plasma insulin at fasting and following an oral glucose load and blood pressure after glucose load in 367 (247 non-obese, 120 obese) normotensive and untreated mildly hypertensive subjects. Overall, there was no independent association between fasting plasma insulin levels and blood pressure values. After controlling for age and body weight, a significant relationship between postglucose plasma insulin levels and diastolic blood pressure was found. When non-obese and obese subjects were examined separately, significant relationships were identified between postglucose plasma insulin levels and both systolic and diastolic blood pressure values in the former but not in the latter. A comparison of sex-, age-, and weight-matched hyperinsulinaemic vs normoinsulinaemic subjects showed that the former had significantly higher values of blood pressure only if not obese. These results demonstrate that the plasma insulin response to glucose is independently correlated with blood pressure.

IGF-1, the Cross Road of the Nutritional, Inflammatory and Hormonal Pathways to Frailty

The decline in functional capacity is a heterogeneous phenomenon in the elderly. An accelerated ageing determines a frail status. It results in an increased vulnerability to stressors for decreased physiological reserves. The early identification of a frail status is essential for preventing loss of functional capacity, and its clinical consequences. Frailty and mobility limitation result from an interplay of different pathways including multiple anabolic deficiency, inflammation, oxidative stress, and a poor nutritional status. However, the age-related decline in insulin-like growth factor 1 (IGF-1) bioactivity deserves special attention as it could represent the ideal crossroad of endocrine, inflammatory, and nutritional pathways to frailty. Several minerals, namely magnesium, selenium, and zinc, appear to be important determinants of IGF-1 bioactivity. This review aims to provide an overview of the potential usefulness of nutrients modulating IGF-1 as potential therapeutic targets in the prevention of mobility limitation occurring in frail older subjects.

SHBG, Sex Hormones, and Inflammatory Markers in Older Women

CONTEXT In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. OBJECTIVE The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. DESIGN AND PATIENTS We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. RESULTS In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. CONCLUSION In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state.

Gonadal status and physical performance in older men

Objective. To test the relationship between gonadal status and objective measures and determinants of physical performance in older men and their determinants. Methods. The study included 455 ≥ 65 year older men of InCHIANTI study, Italy, with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance. Results. Three different groups of older men were created: (1) severely hypogonadal (N = 23), total testosterone levels ≤230 ng /dl; (2) moderately hypogonadal (N = 88), total testosterone >230 and < 350 ng/dl) and (3) eugonadal (N = 344), testosterone levels ≥350 ng/dl. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in haemoglobin levels, hand grip strength and SPPB score (p for trend < 0.001) among three groups, with severely hypogonadal men having lower values of haemoglobin, muscle strength and physical performance. We found no association between testosterone group assignment and calf muscle mass and 4 m walking speed. In the multivariate analysis grip strength (p for trend = 0.004) and haemoglobin (p for trend < 0.0001) but not SPPB and other determinants of physical performance were significantly different between the three groups. Conclusions. In older men, gonadal status is independently associated with some determinants (haemoglobin and muscle strength) of physical performance.

Influence of the menstrual cycle on glucose tolerance and insulin secretion

To evaluate the impact of the menstrual cycle on glucose tolerance and insulin secretion, in the present study we have measured the plasma concentrations of glucose, insulin, and C-peptide during a 2-hour oral glucose tolerance test in 110 healthy, nonobese, regularly menstruating women. Fifty-five women were in the follicular phase, and 55 were in the luteal phase of the cycle. The two groups were well matched for age and body weight. Plasma concentrations of glucose, insulin, and C-peptide either in the fasting state or after the oral glucose load did not differ in the two groups. These results suggest that in nondiabetic women the menstrual cycle has no major effect on glucose tolerance and insulin secretion and that the phase of the menstrual cycle should not be considered in programming and interpreting an oral glucose tolerance test.

Vitamin D in older population: new roles for this ‘classic actor’?

Vitamin D is a group of lipophilic hormones with pleiotropic actions. It has been traditionally related to bone metabolism, although several studies in the last decade have suggested its role in muscle strength and falls, cardiovascular and neurological diseases, insulin-resistance and diabetes, malignancies, autoimmune diseases and infections. Vitamin D appears to be a hormone with several actions and is fundamental for many biological systems including bone, skeletal muscle, brain and heart. The estimated worldwide prevalence of vitamin D deficiency of 50% in elderly subjects underlines the importance of vitamin D deficiency for public health. In this review, we will describe changes in vitamin D levels with age in both sexes, cut off values to define Vitamin D status, the impact of vitamin D deficiency in age-related disease and finally different therapeutic options available to treat Vitamin D deficiency in older populations.

Association of plasma selenium concentrations with total IGF-1 among older community-dwelling adults: the InCHIANTI study.

BACKGROUND & AIMS Insulin-like growth factor (IGF-1) stimulates cell proliferation and inhibits cell apoptosis. Recent studies underline its importance as anabolic hormone and nutritional marker in older individuals. IGF-1 synthesis and bioactivity are modulated by nutritional factors including selenium intake. However, whether circulating IGF-1 levels are positively influenced by plasma selenium, one of the most important human antioxidants, is still unknown. METHODS Selenium and total IGF-1 were measured in 951 men and women ≥ 65 years from the InCHIANTI study, Tuscany, Italy. RESULTS Means (SD) of plasma selenium and total IGF-1 were 0.95 (0.15) μmol/L and 113.4 (31.2)ng/mL, respectively. After adjustment for age and sex, selenium levels were positively associated with total IGF-1 (β±SE: 43.76±11.2, p=0.0001). After further adjustment for total energy and alcohol intake, serum alanine aminotransferase (ALT), congestive heart failure, selenium remained significantly associated with IGF-1 (β±SE: 36.7±12.2, p=0.003). The association was still significant when IL-6 was introduced in the model (β±SE: 40.1±12.0, p=0.0008). CONCLUSIONS We found an independent, positive and significant association between selenium and IGF-1 serum levels in community dwelling older adults.

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly.

Evidence for Unimpaired Pancreatic Secretion and Hepatic Removal of Insulin in Healthy Offspring of Type 2 (Noninsulin-Dependent) Diabetic Couples

The aim of the present study was to investigate the secretion and the hepatic removal of insulin in a group of 14 unaffected offspring of 14 type 2 (noninsulin-dependent) diabetic couples compared to 14 healthy subjects without family history of diabetes mellitus. The two groups, each consisting of 5 obese and 9 nonobese subjects, were carefully matched for sex, age, and body weight. We examined glucose, insulin, and C-peptide levels, as well as C-peptide to insulin ratios and relations during the oral glucose tolerance test. Glucose concentrations and incremental areas were similar in the two groups, as well as insulin and C-peptide levels and areas. C-peptide to insulin molar ratios, both in fasting state and after glucose load, as well as relations between C-peptide and insulin incremental areas were not different. Our results suggest that the healthy offspring of type 2 diabetic couples have a normal response of beta-cell to oral glucose as well as a normal removal of insulin by the liver.