The growing incidence of prediabetes and clinical type 2 diabetes, in part characterised by insulin resistance, is a critical health problem with consequent devastating personal and health-care costs. Vitamin D status, assessed by serum 25-hydroxyvitamin D levels, is inversely associated with diabetes in epidemiological studies. Several clinical intervention studies also support that vitamin D, or its active metabolite 1,25-dihydroxyvitamin D (1,25(OH) 2 D), improves insulin sensitivity, even in subjects with glucose metabolism parameters classified within normal ranges. The mechanisms proposed which may underlie this effect include potential relationships with improvements in lean mass, regulation of insulin release, altered insulin receptor expression and specific effects on insulin action. These actions may be mediated by systemic or local production of 1,25(OH) 2 D or by suppression of parathyroid hormone, which may function to negatively affect insulin sensitivity. Thus, substantial evidence supports a relationship between vitamin D status and insulin sensitivity; however, the underlying mechanisms require further exploration. Vitamin D: Diabetes: Insulin sensitivity: Insulin resistanceThe reported incidence of diabetes is increasing at an alarming rate. The WHO estimates that more than 180 million individuals worldwide have diabetes and that 1·1 million died from diabetes in 2005 (1) . Further, the WHO estimates that this number is likely to more than double by 2030 (1) . The rate of change in incidence of insulin resistance and diabetes cannot be accounted for by shifts in population demographics, which suggests that lifestyle choices, rather than differences in genetics, are a primary contributor. Unfortunately, the dramatic rise in the prevalence of diabetes in this decade is likely to continue given the number of Americans with prediabetes and given that current recommendations for prevention are either ineffective or are not implemented sufficiently.Several lifestyle factors may play a role in this rapid increase in prediabetes and progression to clinical diabetes. An increase in diabetes has occurred concurrently with an increase in obesity, as the latter is a strong risk factor for diabetes. This relationship may be rooted in the general relationship between energy balance, obesity and diabetes. However, the presence, or absence, of specific dietary factors may also play a role in these diseases. Therefore it is critical to identify factors that influence body weight, factors that are independent of weight that will contribute to the prevention of abnormal glucose homeostasis and insulin resistance to reduce the incidence of diabetes beyond the difficult process of weight loss. It has been proposed that vitamin D may play an important role in the development of insulin resistance and diabetes (2 -4) . Although low vitamin D status is also implicated in the development of type 1 diabetes (or insulin-dependent diabetes) diabetes (5) , the present review will focus on the relationship of vitamin D sta...

Regardless of exercise group assignment, calcium adjusted for energy intake had a negative relationship and vitamin A intake a positive relationship with two year changes in total body weight and body fat in young women aged 18 to 31 years. Thus, subjects with high calcium intake, corrected by total energy intake, and lower vitamin A intake gained less weight and body fat over two years in this randomized exercise intervention trial.

SummaryWe established the role for epigenetics in regulation of NOTCH signaling in breast cancer. This may constitute a common mechanism of activation of oncogenic signals. Our study provides support for epigenetic-targeting strategies in anticancer approaches.

An algorithm was developed to estimate the strength of the femoral neck from data generated by the dual-energy x-ray absorptiometry (DXA). This algorithm considers shape of the proximal femur as well as cross-sectional moment of inertia (CSMI) in the estimate. Proximal femora (10) from cadavers of white adults and an aluminum step wedge were scanned with the Lunar DPX to validate the calculation of CSMI. After scanning, each femoral neck was sectioned at its narrowest portion for direct measurement of CSMI. Three healthy young women were scanned five times each to evaluate the reproducibility of geometric measurements using DXA. There was a strong linear association between the CSMI measured directly and using DXA in both cadaver bones (r2 = 0.96) and the aluminum step wedge (r2 = 0.99). The coefficient of variation for CSMI from repeated measurements using DXA was less than 3%. This indicates that it is possible to estimate reproducibly the bending rigidity of bone from DXA measurements. The data from 306 normal subjects were analyzed to investigate geometric changes in the femoral neck with age. Although there was no strong correlation between CSMI and age in normal subjects of either sex, safety factor (SF, an index of strength of the femoral neck during walking) and fall index (FI, an index of the strength of the femoral neck during a fall) decrease with age in both sexes. We observed an alteration of the geometric structure of the femoral neck with age that may increase the stress on the femoral neck and decrease SF and FI.

High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1α,25-dihydroxyvitamin D hydroxylase (1α-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) from the substrate 25-hydroxyvitamin D (25OHD). Expression and dietary regulation of 1α-hydroxylase in tissues associated with energy metabolism, including adipose tissue, has not been assessed. Male Wistar rats were fed a high calcium (1.5%) and high vitamin D (10,000 IU/kg) or a low calcium (0.25%), low vitamin D (400 IU/kg) with either a high fat (40% energy) or high sucrose (66% energy) dietary background for 14 weeks. Expression of 1α-hydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1α-hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 25OHD treatment at 10 nM levels induced 1,25(OH)2D responsive gene, CYP24, and this response was reduced in the presence of the p450 inhibitor, ketoconazole. In addition, 3H 25OHD was converted to 3H 1,25(OH)2D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that 1α-hydroxylase is expressed in adipose tissue and is functional in cultured adipocytes. Thus, the capacity for local production may play a role in regulating adipocyte growth and metabolism.

Objective: The purpose of this study was to investigate the impact of dietary calcium or dairy product intake on total energy expenditure (TEE), fat oxidation, and thermic effect of a meal (TEM) during a weight loss trial. Methods and Procedures:The intervention included a prescribed 500-kcal deficit diet in a randomized placebo-controlled calcium or dairy product intervention employing twenty-four 18 to 31-year-old (22.2 ± 3.1 years, mean ± s.d.) overweight women (75.5 ± 9.6 kg). TEM and fat oxidation were measured using respiratory gas exchange after a meal challenge, and TEE was measured by doubly labeled water. Fat mass (FM) and lean mass (fat-free mass (FFM)) were measured by dual-energy X-ray absorptiometry. Subjects were randomized into one of these three intervention groups: (i) placebo (<800 mg/day calcium intake); (ii) 900 mg/day calcium supplement; (iii) three servings of dairy products/day to achieve an additional 900 mg/day. Results: There were no group effects observed in change in TEE; however, a group effect was observed for fat oxidation after adjusting for FFM (P = 0.02). The treatment effect was due to an increase in fat oxidation in the calcium-supplemented group of 1.5 ± 0.6 g/h, P = 0.02. Baseline 25-hydroxyvitamin D (25OHD) was positively correlated with TEM (R = 0.31, P = 0.004), and trended toward a correlation with fat oxidation (P = 0.06), independent of group assignment. Finally, the change in log parathyroid hormone (PTH) was positively correlated with the change in trunk FM (R = 0.27, P = 0.03). Discussion: These results support that calcium intake increases fat oxidation, but does not change TEE and that adequate vitamin D status may enhance TEM and fat oxidation.

A 12-week randomized controlled multi-center clinical trial was conducted in 106 overweight and obese adults. Diets were designed to produce a 2,093 kJ/day energy deficit with either low calcium (LC; ~600 mg/day), high calcium (HC; ~1,400 mg/day), or high dairy (HD; three dairy servings, diet totaling ~1,400 mg/day). Ninety-three subjects completed the trial, and 68 met all a priori weekly compliance criteria. Both HC and HD contained comparable levels of calcium, but HC was only ~30% as effective as HD in suppressing 1,25-(OH)2D and exerted no significant effects on weight loss or body composition compared to LC. In the group that met compliance criteria, HD resulted in ~two-fold augmentation of fat loss compared to LC and HC (HD: -4.43 ± 0.53 kg; LC: -2.69 ± 0.0.53 kg; HC: -2.23 ± 0.73kg, p < 0.025); assessment of all completers and an intent-to-treat analysis produced similar trends. HD augmentated central (trunk) fat loss (HD: -2.38 ± 0.30 kg; HC: -1.42 ± 0.30 kg; LC: -1.36 ± 0.42 kg, p < 0.05) and waist circumference (HD: -7.65 ± 0.75 cm; LC: -4.92 ± 0.74 cm; LC: -4.95 ± 1.05 cm, p < 0.025). Similar effects were noted among all subjects completing the study and in an intent-to-treat analysis. These data indicate that dairy-rich diets augment weight loss by targeting the fat compartment during energy restriction.

Increased intake of dairy products does not alter body weight or fat mass in young, healthy women over 1 y.