Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies.

Individuals with diabetes mellitus (DM) have an increased risk of fracture. Glycemic control is crucial to the management of DM, but there are concerns pertaining to hypoglycemia development in the course of glycemic control target achievement. The extent to which glycemic control may affect the risk of fracture remains less defined. Hypoglycemia-induced falls have been suggested to contribute to an elevated risk of fracture in DM patients. In this meta-analysis of observational studies, we aimed to investigate the relative contribution of glycemic control, as measured by glycated hemoglobin (HbA1c), and hypoglycemia to the risk of fracture in DM. The PubMed and Web of Science databases were searched for relevant studies. A random-effects model was used to generate summary relative risks (RRs) and 95% confidence intervals (CIs). Both increased HbA1c levels (RR per 1% increase 1.08, 95% CI 1.03, 1.14; nstudies = 10) and hypoglycemia (RR 1.52, 95% CI 1.23, 1.88; nstudies = 8) were associated with an increased risk of fracture. The association between HbA1c levels and the risk of fracture was somewhat nonlinear, with a noticeably increased risk observed at an HbA1c level ≥ 8%. The positive associations of HbA1c levels and hypoglycemia with the risk of fracture did not reach statistical significance in the studies that adjusted for insulin use, hypoglycemia, or falls for the former and in those that adjusted for falls for the latter. In summary, both increased HbA1c levels and hypoglycemia may increase the risk of fracture in patients with DM. The positive association between HbA1c levels and the risk of fracture appears to be, in part, explained by hypoglycemia-induced falls, possibly due to insulin use. The avoidance of hypoglycemia in the course of achieving good glycemic control through the careful selection of glucose-lowering medications may contribute to fracture prevention by reducing the risk of falls related to treatment-induced hypoglycemia.

Systematic review and meta-analysis of the association between dairy consumption and the risk of hip fracture: critical interpretation of the currently available evidence.

In the present meta-analysis, reductions in the risk of hip fracture with milk consumption were only observed among American adults, but not among Scandinavian adults, possibly because milk products are more commonly fortified with vitamin D in the former population than in Scandinavian countries. The reduction in the risk of hip fracture was also observed with yogurt consumption, which is often associated with healthy lifestyles and dietary patterns that contribute to improved bone health. INTRODUCTION: Although dairy products contain bone-beneficial nutrients, the association between dairy consumption and the risk of hip fracture remains equivocal. Fueling this uncertainty, the elevated risk of hip fracture in association with milk consumption was observed in a cohort of Swedish women. A systematic review and meta-analysis of prospective cohort studies was performed to critically evaluate the association, or lack thereof, between dairy consumption (milk, yogurt, and cheese) and the risk of hip fracture. METHODS: A random effects model was used to generate the summary relative risks (RRs) with their 95% confidence intervals (CIs) for the associations of interest. RESULTS: In the meta-analysis of the highest versus lowest category of consumption, higher consumption of yogurt (RR 0.78, 95% CI 0.68, 0.90), but not milk (RR 0.86, 95% CI 0.73, 1.02) or cheese (RR 0.85, 95% CI 0.66, 1.08), was associated with a lower risk of hip fracture. For milk, the reduced risk of fracture with higher milk consumption was observed in the USA (RR 0.75, 95% CI 0.65, 0.87), but not in Scandinavian countries (RR 1.00, 95% CI 0.85, 1.17). These findings were further supported by the fact that American studies (RR 0.93, 95% CI 0.88, 0.98; per 1 glass/day), but not Scandinavian studies (RR 1.01, 95% CI 0.95, 1.07; per 1 glass/day), demonstrated a linear association between milk consumption and the risk of hip fracture. CONCLUSIONS: The cumulative evidence from prospective cohort studies reassuringly suggests that the risk of hip fracture may not be elevated among people who consume milk, yogurt, and cheese, and that a greater consumption of milk or yogurt may even be associated with a lower risk of hip fracture depending on the factors that may differ across the population of interest.

Effects of early protein restriction on the growth performance and gut development of pigs fed diets with or without antibiotic.

In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.

Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in real-world use: systematic review and meta-analysis of observational studies.

In the present meta-analysis based on real-world data, the use of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1ra), or sodium-glucose cotransporter-2 inhibitors (SGLT2i) was not associated with the risk of fracture. INTRODUCTION: Cumulative evidence from randomized control trials (RCTs) with limited fracture events showed that the use of DPP-4i, GLP-1ra, or SGLT2i may not affect the risk of fracture. However, additional insights from large population-based studies with routinely collected data on fracture events and an adequate amount of fracture events are necessary to draw firm conclusions. To refine and complement the results from RCTs, a systematic review and meta-analysis of observational studies were performed to investigate the association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture in real-world settings. METHODS: The PubMed and Web of Science databases were searched to identify relevant observational studies. A random-effect model was used to estimate the summary relative risks (RRs). RESULTS: The use of DPP-4i (RR 0.83, 95% CI [confidence interval] 0.60, 1.14; n = 11), GLP-1ra (RR 0.65, 95% CI 0.24, 1.74; n = 4), or SGLT2i (RR 1.02, 95% CI 0.91, 1.16; n = 4) was not associated with the risk of fracture. In general, there was a consistent lack of association between the use of DPP-4i or GLP-1ra and the risk of fracture across nearly all subgroups, except for a significantly reduced risk of hip fracture with the use of GLP-1ra (RR 0.21, 95% CI 0.04, 0.98). CONCLUSIONS: Cumulative real-world evidence does not support an association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture. Our findings, together with the cumulative evidence from RCTs, should reassure policy makers and medical practitioners that the use of these medications is unlikely to increase the risk of fracture among type 2 diabetes mellitus patients in general. Further studies need to investigate the long-term impact of these drugs on the fracture risk, particularly in high-risk populations.

Sex hormone-binding globulin and risk of fracture in older adults: systematic review and meta-analysis of observational studies.

We conducted a meta-analysis of observational study to clarify the association between sex hormone-binding globulin (SHBG) levels and the risk of fracture in older adults. We found that higher SHBG levels were associated with an increased risk of fracture in older adults. INTRODUCTION: The association between SHBG levels and the risk of fracture in older adults remains elusive. We aim to clarify this association by conducting a meta-analysis of observational studies. METHODS: PubMed and Web of Science databases were searched for relevant observational studies investigating the association between SHBG levels and the risk of fracture in older adults. The relative risks (RRs) with 95% confidence intervals (CIs) from each study were transformed into a continuous variable for each 1 µg/dL increase in SHBG and were pooled under a random-effects model. RESULTS: A total of 16 observational studies were included in the present meta-analysis. The summary RR of fracture risk associated with each 1 µg/dL increase in SHBG was 1.18 (95% CI 1.11, 1.26); no statistically significant heterogeneity was observed across studies (I2 = 0%, P = 0.67). The positive association was also evident in men (RR 1.22, 95% CI 1.12, 1.33) and women (RR 1.15, 95% CI, 1.05, 1.26). By site of fracture, higher SHBG levels were positively associated with higher risks of hip fracture (RR 1.43, 95% CI 1.23, 1.65), vertebral fracture (RR 1.31, 95% CI 1.12, 1.54), and non-vertebral fracture (RR 1.21, 95% CI 1.06, 1.38). CONCLUSIONS: The present meta-analysis suggests that higher SHBG levels predict an increased risk of fracture in older adults. Further studies should aim to elucidate the complex biological mechanisms by which SHBG may affect fracture risk.

Body fatness at a young age and risks of eight types of cancer: systematic review and meta-analysis of observational studies.

The associations between body fatness at a young age (childhood, adolescence and young adulthood; age ≤ 30 years) and diffuse large B-cell lymphoma (DLBCL), oesophageal adenocarcinoma, gastric cardia cancer, hepatocellular carcinoma, multiple myeloma, pancreatic cancer, renal cell cancer and thyroid cancer remain inconclusive. We performed a comprehensive systematic literature review and meta-analysis of observational studies to clarify the associations between body fatness at a young age and the risks of these cancers. PubMed and Web of Science databases were searched for relevant observational studies. Fifty-six articles yielded data on 27,559 cancer cases, including 3,170 DLBCL, 1,491 oesophageal adenocarcinoma, 1,103 gastric cardia cancer, 1,067 hepatocellular carcinoma, 3,090 multiple myeloma, 7,220 pancreatic cancer, 6,212 renal cell cancer and 4,206 thyroid cancer cases. Each 5 kg m-2 increase in body mass index at a young age was positively associated with DLBCL (relative risk [RR] 1.21, 95% confidence interval [CI] 1.09, 1.35), oesophageal adenocarcinoma (RR 1.88, 95% CI 1.37, 2.57), gastric cardia cancer (RR 1.59, 95% CI 1.15, 2.21), hepatocellular carcinoma (RR 1.31, 95% CI 1.13, 1.51), multiple myeloma (RR 1.23, 95% CI 1.15, 1.30), pancreatic cancer (RR 1.17, 95% CI 1.11, 1.24), renal cell cancer (RR 1.22, 95% CI 1.16, 1.28) and thyroid cancer (RR 1.12, 95% CI 1.07, 1.17). In summary, higher body fatness at a young age increases the risks of developing various types of cancer later in life. Prevention of overweight and obesity in children, adolescents and young adults should therefore be emphasized to reverse the obesity epidemic and thereby avoid further increases in the burden of cancer attributed to excess body fatness.

Body fatness at a young age, body fatness gain and risk of breast cancer: systematic review and meta-analysis of cohort studies.

Higher body fatness in adulthood has been consistently associated with an increased risk of postmenopausal breast cancer, as well as a tendency towards a lower risk of premenopausal breast cancer. However, the association between body fatness at a young age (≤30 years), body fatness gain and the risk of breast cancer is less defined. PubMed and Web of Science databases were searched to identify relevant publications. Risk estimates with 95% confidence intervals from each study were transformed into a continuous variable for each 5 kg m-2 increase in body mass index (BMI) and were pooled under a random-effects model. Each 5 kg m-2 increase in BMI was significantly associated with a 14%, 12% and 17% lower risk of breast cancer later in life among all women, premenopausal women and postmenopausal women, respectively. Significant heterogeneity and publication bias were observed. The results remained unchanged after the trim and fill method was applied to correct the bias. Each 5 kg m-2 increase in BMI from a young age until cohort entry was significantly associated with a 13% and 14% higher risk of breast cancer in all women and postmenopausal women, respectively. In summary, higher body fatness at a young age may have a protective role in the later development of breast cancer in both premenopausal and postmenopausal women. However, this potential benefit should not be overemphasized, as our findings suggest that increased body fatness gain from a young age is positively associated with postmenopausal breast cancer risk. These findings further justify the need to maintain a steady weight throughout life.

Dietary linseed oil in the maternal diet affects immunoglobulins, tissue fatty acid composition and expression of lipid metabolism-related genes in piglets.

This experiment investigated the effects of supplementing the maternal diet with linseed oil (LSO) and soya bean oil (SBO) on immunoglobulins, the fatty acid composition and hepatic expression of lipid metabolism-related genes in piglets. Multiparous sows (twenty-four per diet) were fed on diets containing a supplement of either SBO or LSO during last week of gestation and lactation. The results indicated that supplementation of maternal diet with LSO could improve the weaning weight of piglets and average daily gain (ADG) (p < 0.05). The concentration of immunoglobulin G (IgG) and immunoglobulin A (IgA) was enhanced in sow plasma, colostrum and milk by the addition of LSO (p < 0.05). In addition, the concentration of 18: 3n-3 fatty acids was higher in the milk of LSO sows. Meanwhile, maternal supplementation with LSO increased the levels of plasma IgG, IgA and the tissues n-3 polyunsaturated fatty acid (PUFA) in piglets (p < 0.05). Correspondingly, the mRNA expression levels of hepatic ∆5-desaturase (D5D) and ∆6-desaturase (D6D) were higher, and fatty acid synthase (FAS) was lower in piglets from LSO-fed sows when compared with that in the SBO group. In conclusion, LSO supplementation of the maternal diet increases immunoglobulins, modifies the fatty acid composition and affects the gene of D5D and D6D expression of piglets.

Effects of feeding sodium stearoyl-2-lactylate diets to lactating sows on performance, digestibility of nutrients, composition, and fat globule size in milk.

The objective of this study was to determine the effects of feeding sodium stearoyl-2-lactylate (SSL) as a new feeding emulsifier diet with and without soybean oil (SO) on the milk fat globule (MFG) size, milk composition, digestibility of nutrients, and performance in lactating sows. Sixty sows (Large White × Landrace) were randomly assigned to 1 of 4 treatments according to a 2 × 2 factorial arrangement of treatments. Each treatment had 15 replicates composed of 1 sow. The factors included 1) the fat level (0% vs. 3% SO) and 2) the emulsifier content (0% vs. 0.1% SSL). Treatments included 1) Control (without SO and SSL), 2) SO (3% SO without SSL), 3) SSL (0.1% SSL without SO), and 4) SO + SSL (3% SO and 0.1% SSL). During the suckling period, sows in the SO + SSL group lost less back fat thickness ( < 0.05) compared to other groups; sows fed 3% SO diets consumed less feed ( < 0.05) compared to sows fed diets without SO, but there were no significant effects ( > 0.05) of dietary fat and its interaction with a dietary emulsifier on energy intake and the weaning-estrus interval. The digestibility of ether extract in the SO + SSL group was greater than in the SO group ( < 0.05). Moreover, greater digestibility of CP, Ca, and P in the SO+SSL group was observed compared to that of other groups ( < 0.05). Feeding the SO + SSL diet improved the concentrations of milk fat, protein, and total solids on d 11 of lactation compared to other diets ( < 0.05). Also, an interaction between supplemental SSL and SO was observed for the milk fat and total solids concentrations. The average diameter of MFG on d 11 of lactation was significantly decreased by the addition of 0.1% SSL compared to a diet with no SSL supplementation ( < 0.05). No significant differences among the dietary treatments were observed in cholesterol, triglyceride, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol in sows' plasma ( > 0.05). In conclusion, feeding a 0.1% SSL diet to lactating sows may decrease the average diameter of MFG and improve the digestibility of nutrients and composition of milk.

Effects of conjugated linoleic acid or betaine on the growth performance and fatty acid composition in backfat and belly fat of finishing pigs fed dried distillers grains with solubles.

The objectives of this study were to determine the effects of conjugated linoleic acid (CLA) or betaine on the growth performance, carcass characteristics and fatty acid composition in backfat and belly fat of pigs fed distillers dried grains with solubles (DDGS). Thirty-two (60±2 kg) crossbred barrows (Duroc×Landrace×Yorkshine) were assigned to one of four diets randomly: (1) the control diet containing no corn DDGS (control group); (2) the diet containing 30% corn DDGS (DDGS-fed group); (3) the diet containing 30% corn DDGS and 10 g/kg CLA (CLA-fed group); (4) the diet containing 30% corn DDGS and 1 g/kg BET (BET-fed group). The pigs fed DDGS showed that the percentages of C18:2, polyunsaturated fatty acid (PUFA) and iodine value (IV) increased, while C18:1, saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) decreased. Pigs fed the DDGS+CLA or DDGS+betaine diets showed the increased percentage of SFA, and the decreased percentage of C18:2, PUFA and IV. In conclusion, results confirmed that the diets containing 30% DDGS had no detrimental effects on growth performance, but increased the percentage of PUFA and IV and decreased the percentage of SFA and MUFA in the backfat and belly fat. However, supplementation with CLA or BET can part reverse these effects on carcass fat in finishing pigs.

Correlation of miR-494 expression with tumor progression and patient survival in pancreatic cancer.

MicroRNA-494 (miR-494) expression is aberrant in various types of human cancer. However, the prognostic value of miR-494 in pancreatic cancer remains unclear. The level of miR-494 expression was determined in 99 pairs of primary pancreatic cancer and their corresponding, adjacent non-tumor tissues by using quantitative reverse transcriptase polymerase chain reaction. We also analyzed the associations between miR-494 expression and clinicopathological features. The survival correlations were analyzed by using the Kaplan-Meier method and Cox proportional hazards model. The level of miR-494 expression was significantly downregulated in pancreatic cancer tissues (mean relative expression level ± SD, 0.48 ± 0.11) as compared to matched adjacent normal tissues (1.80 ± 0.28, P < 0.05). We found significant correlations between the miR-494 expression levels and TNM stage (P = 0.009), lymphatic invasion (P = 0.036), vascular invasion (P = 0.011), distant metastasis (P = 0.007), and tumor grade (P = 0.031). Pancreatic cancer patients with a low miR-494 expression level had a shorter overall survival than those with a high miR-494 expression level (P < 0.05). Reduced miR-494 expression in pancreatic cancer tissues is correlated with tumor progression and might be an independent, poor prognostic factor for patients with pancreatic cancer.

Dietary Supplementation of Magnesium Sulfate during Late Gestation and Lactation Affects the Milk Composition and Immunoglobulin Levels in Sows.

This experiment was conducted to investigate the effects of dietary supplementation of magnesium sulfate (MgSO4) during late gestation and lactation on sow and litter performance, fecal moisture, blood biochemistry parameters, immunoglobulin levels and milk composition in sows. Forty-eight sows (Yorkshire×Landrace, 4th to 5th parity) were randomly allocated to 1 of 4 dietary treatments supplemented with 0, 200, 400, or 600 mg/kg MgSO4 (n = 12). The experiment started on day 90 of gestation and continued through day 21 of lactation. Blood samples were collected on day 107 of gestation, day 0 (farrowing) and 21 (weaning) of lactation for the analyses of the blood biochemistry parameters and immunoglobulin levels. The colostrum and milk samples were obtained on day 0 and 14 of lactation, respectively. Fecal samples were collected from the sows on day 107 of gestation as well as day 7 and 20 of lactation to determine fecal moisture content. The results showed that the survival percentage of piglets and the litter weight at weaning were decreased linearly (p<0.05) and other parameters of the sow or litter performance were not influenced (p>0.05) by MgSO4 supplementation. The fecal moisture content of the sows were increased (p<0.05) linearly as dietary MgSO4 increased on day 7 and 20 of lactation. Supplementation with MgSO4 increased the plasma magnesium (Mg) level linearly (p<0.05) and had a trend to increase total protein level (p>0.05 and p<0.10). However, an increase in the dietary MgSO4 level resulted in a linear decrease in the colostrum fat content (p<0.05). Dietary MgSO4 supplementation enhanced the immunoglobulin G (IgG) level (linear, p<0.05) in plasma on day of farrowing and immunoglobulin A (IgA) level in colostrum (quadratic, p<0.05) and milk (linear, p<0.05) of the sows. These results indicated that supplementation with MgSO4 during late gestation and lactation may have the potential to prevent sow constipation, but may also result in some negative effects.

Effectiveness of maifanite in reducing the detrimental effects of cadmium on growth performance, cadmium residue, hematological parameters, serum biochemistry, and the activities of antioxidant enzymes in pigs.

This study was conducted to investigate the toxicity of cadmium and to evaluate the effectiveness of maifanite in preventing cadmium-induced adverse effects. Thirty-two crossbred pigs (Duroc × Landrace × Large white, sex balanced, 17.25 ± 0.07 kg average body weight) were randomly allotted to one of four dietary treatments in a 2 × 2 factorial arrangement, with eight replicates per treatment and one pig per replicate. The dietary treatments included two cadmium (as CdCl2) doses (0.32 and 30.49 mg/kg) and two maifanite doses (0 and 1%). The results showed that pigs treated with cadmium decreased their average daily feed intake (P < 0.05) and increased (P < 0.05) the feed/gain ratio. Cadmium was found in the tissues of pigs that were fed with cadmium-contaminated diets, but the level of cadmium was much lower when maifanite was added to the cadmium-contaminated diets. Ingestion of diets that were artificially contaminated with cadmium (30.49 mg/kg of cadmium) reduced (P < 0.05) the number of lymphocytes, the total erythrocyte count, the hemoglobin level, and the hematocrit. However, the activities of serum aspartate aminotransferase and gamma glutamyltransferase were increased (P < 0.05). The total protein level was lower (P < 0.05) in pigs fed with cadmium-contaminated diets. The contents of malondialdehyde increased (P < 0.05), while the total antioxidant capacity and the activities of total superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and catalase decreased (P < 0.05) in pigs fed with cadmium-contaminated diets. Dietary addition of maifanite can, to some extent, prevent the negative effects associated with feeding cadmium diets (30.49 mg/kg of cadmium) to pigs.