Metabolic Bone Disease in Children with Intestinal Failure and Long-Term Parenteral Nutrition: A Systematic Review

Metabolic bone disease (MBD) is a possible complication of intestinal failure (IF), with a multi-factorial pathogenesis. The reduction of bone density (BMD) may be radiologically evident before manifestation of clinical signs (bone pain, vertebral compression, and fractures). Diagnosis relies on dual-energy X-ray absorptiometry (DXA). Incidence and evolution of MBD are not homogeneously reported in children. The aim of this systematic review was to define the prevalence of MBD in IF children and to describe risk factors for its development. A comprehensive search of electronic bibliographic databases up to December 2021 was conducted. Randomized controlled trials; observational, cross-sectional, and retrospective studies; and case series published between 1970 and 2021 were included. Twenty observational studies (six case-control) were identified and mostly reported definitions of MBD based on DXA parameters. Although the prevalence and definition of MBD was largely heterogeneous, low BMD was found in up to 45% of IF children and correlated with age, growth failure, and specific IF etiologies. Data demonstrate that long-term follow-up with repeated DXA and calcium balance assessment is warranted in IF children even when PN dependence is resolved. Etiology and outcomes of MBD will be better defined by longitudinal prospective studies focused on prognosis and therapeutic perspectives.     

Metabolic Profile and Bone Status in Post-Menopausal Women with Rheumatoid Arthritis: A Monocentric Retrospective Survey

Background: Rheumatoid arthritis (RA) and metabolic syndrome (MetS) are chronic conditions that share common inflammatory mechanisms. Both diseases can lead to an impairment of the bone microarchitecture. The aims of our study were to evaluate clinical, metabolic, and bone parameters in RA patients with or without MetS (MetS+, MetS−) and potential correlations between the glico-lipidic profile, RA disease activity, and bone status. Methods: A total of thirty-nine RA female post-menopausal patients were recruited (median age 66.6 ± 10.4, disease duration 3 ± 2.7). Anthropometric data, medical history, and current treatment were recorded along with basal blood tests, bone, and lipid metabolism biomarkers. RA disease activity and insulin resistance were evaluated through standard scores. Quantitative assessment of the bone (bone mineral density—BMD) was performed by dual-energy-X ray absorption (DXA), whereas bone quality was quantified with the trabecular bone score (TBS). Results: No statistically significant differences concerning both BMD and TBS were detected between the MetS+ and MetS− RA patients. However, the MetS+ RA patients exhibited significantly higher disease activity and lower serum 25-hydroxyvitamin D [25(OH)D] concentrations (respectively, p = 0.04 and p = 0.01). In all RA patients, a significant negative correlation emerged between the BMD of the femoral trochanter with plasmatic triglycerides (TG) concentrations (r = −0.38, p = 0.01), whereas the lumbar BMD was positively correlated with the abdominal waist (AW) and fasting glucose (FG) concentrations. On the other hand, the TBS was negatively correlated with insulin concentrations, FG, and RA disease activity (respectively, r = −0.45, p = 0.01, r = −0.40, p = 0.03, r = −0.37, p = 0.04), the last one was further negatively correlated with 25-OHD serum concentrations (r = −0.6, p = 0.0006) and insulin-resistance (r = 0.3, p = 0.04). Conclusions: Bone quantity (BMD) and quality (TBS) do not seem significantly changed among MetS+ and MetS− RA patients; however, among MetS+ patients, both significantly higher disease activity and lower vitamin D serum concentrations were observed. In addition, the significant negative correlations between the alterations of metabolic parameters limited to the TBS in all RA patients might suggest that qualitative bone microarchitecture impairments (TBS) might manifest despite unchanged BMD values.     

A Three-Year Longitudinal Study Comparing Bone Mass,Density, and Geometry Measured by DXA,pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15 years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm²), bone mineral apparent density (L2–L4 BMAD g/cm³) and total body less head BMDa (TBLH g/cm²). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.     

Suboptimal Plasma Vitamin C Is Associated with Lower Bone Mineral Density in Young and Early Middle-Aged Men: A Retrospective Cross-Sectional Study

Background: This study was conducted to evaluate associations between bone mineral density (BMD) and four selected circulating nutrients, particularly vitamin C, among adults aged 20–49 years. Methods: In this retrospective cross-sectional study, the lumbar spine BMD of 866 men and 589 women were measured by dual-energy X-ray absorptiometry and divided into tertiles, respectively. Logistic regressions were used to identify the predictors of low BMD by comparing subjects with the highest BMD to those with the lowest. Results: Multivariate logistic regressions identified suboptimal plasma vitamin C (adjusted odds ratio (AOR) 1.64, 95% confidence interval (CI) 1.16, 2.31), suboptimal serum vitamin B12 (AOR 2.05, 95% CI 1.02, 4.12), and low BMI (BMI < 23) (AOR 1.68, 95% CI 1.12, 2.53) as independent predictors for low BMD in men. In women, low BMI was the only independent predictor for low BMD. Plasma vitamin C, categorized as suboptimal (≤8.8 mg/L) and sufficient (>8.8 mg/L), was positively significantly correlated with the lumbar spine BMD in men, but there was no association in women. Conclusions: Plasma vitamin C, categorized as suboptimal and sufficient, was positively associated with the lumbar spine BMD in young and early middle-aged men. A well-designed cohort study is needed to confirm the findings.     

Increased Plasma Concentrations of Vitamin D Metabolites and Vitamin D Binding Protein in Women Using Hormonal Contraceptives: A Cross-Sectional Study

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25–35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)₂D) (198 [163-241] vs. 158 [123-183] pmol/L, p = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)₂D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%–25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites.     

Vitamin E Improves Serum Paraoxonase-1 Activity and Some Metabolic Factors in Patients with Type 2 Diabetes: No Effects on Nitrite/Nitrate Levels

Objective: It is known that markers of oxidative stress and nitrite/nitrate anion (NO_x) increase and activity of antioxidative enzyme paraoxonase-1 decline in type 2 diabetes mellitus (DM). The effects of vitamin E on paraoxonase-1 activity and NO_x in patients with type 2 diabetes are not known. The purpose of this study was to examine the hypothesis that vitamin E supplementation would affect paraoxonase-1 activity, metabolic factors, and NO_x in patients with DM.

Methods: This double-blind, randomized, controlled clinical trial was conducted on 83 patients with DM aged 30–60 years. Forty-two of the subjects had taken 400 IU/day vitamin E and 41 were given placebo over 8 weeks. Fasting blood samples, anthropometric measurements, and dietary intake data were collected at the baseline and at the end of the trial.

Results: Vitamin E significantly increased serum vitamin E level, paraoxonase-1 activity, and total antioxidant status (TAS) and decreased fasting blood sugar (FBS) compared to the control group (p < 0.05). Hemoglobin A1c, serum insulin, and insulin resistance significantly decreased in the vitamin E group compared to baseline values (p < 0.05). Alterations in serum levels of malondialdehyde and NO_x were not significant in any of groups (p > 0.05).

Conclusions: Vitamin E improved serum vitamin E level, paraoxonase-1 activity, TAS, and FBS in patients with type 2 diabetes. Longitudinal studies are warranted to assess the outcome of these results in reducing complications of diabetes in patients with type 2 diabetes.     

The Diabetes Eating Problem Survey-Revised (DEPS-R) in a Greek Adult Population with Type 1 Diabetes Mellitus: Model Comparison Supporting a Single Factor Structure

Type 1 diabetes mellitus (T1DM) patients occasionally develop disordered eating behaviors, leading to insulin manipulation without medical consultation, targeting to achieve weight control. In clinical practice, the Diabetes Eating Problem Survey-Revised Version (DEPS-R) questionnaire has been used to evaluate eating disorders in T1DM patients. This study was conducted to validate the factor structure of the Greek version of DEPS-R using Confirmatory Factor Analysis (CFA), to investigate its reliability and convergent validity in Greek T1DM adults and to compare a single factor DEPS-R model with multiple factor models. Participants were 103 T1DM adults receiving insulin, who responded to DEPS-R. Their anthropometric, biochemical and clinical history data were evaluated. The sample presented good glycemic control and 30.1% scored above the established DEPS-R cut-off score for disturbed eating behavior. CFA results revealed that the data fit well to the factor models. The DEPS-R scale had good reliability and was positively linked to BMI, HbA1c, total daily dose and time in range. Model comparison supported the superiority of the 1-factor model, implying that Greek clinicians and practitioners might not have to consider individualized treatment based on various scores across different subscales but they can adopt a single DEPS-R score for an easy and efficient screening for disordered eating.     

Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.     

Prevalence of Metabolic Syndrome in Children and Adolescents with Type 1 Diabetes Mellitus and Possibilities of Prevention and Treatment: A Systematic Review

Overweight and obesity are an increasingly common problem, not only among the healthy population, but also in adolescents with type 1 diabetes (T1DM). Excess body weight is related to many cardiometabolic complications as well as a high risk of metabolic syndrome (MetS). The purpose of this systematic review is to provide a concise and critical overview of the prevalence of MetS in children and adolescents with T1DM and, ultimately, to discuss prevention and treatment options. The study was conducted in accordance with PRISMA guidelines. This review shows that, apart from the growing percentage of overweight and obese children and adolescents with T1DM (on average 20.1% and 9.5%, respectively), the problem of the increasing incidence of MetS (range from 3.2 to 29.9%, depending on the criteria used) is one of the most important phenomena of our time. One of the methods of prevention and treatment is a combined approach: changing eating habits and lifestyle, but there are also reports about the beneficial effects of the gut microflora.     

Habitual Miso (Fermented Soybean Paste) Consumption Is Associated with Glycemic Variability in Patients with Type 2 Diabetes: A Cross-Sectional Study

Glycemic control, including glycemic variability, is important for the prevention of diabetic vascular complications in patients with type 2 diabetes mellitus (T2DM). There was an association between miso soup intake and insulin resistance. However, the relationship between habitual miso consumption and glycemic control, including glycemic variability, in patients with T2DM remains unknown. We defined people without habitual miso consumption if they did not consume miso soup at all in a day. The average, standard deviation (SD), and coefficient of variation (CV), calculated as CV = (SD/average HbA1c) × 100 (%), of hemoglobin (Hb) A1c levels were evaluated. The proportions of habitual miso consumption of male and female were 88.1% and 82.3%, respectively. The average (7.0 [6.4–7.5] vs. 7.3 [6.8–8.4] %, p = 0.009), SD (0.21 [0.12–0.32] vs. 0.37 [0.20–0.72], p = 0.004), and CV (0.03 [0.02–0.04] vs. 0.05 [0.03–0.09], p = 0.005) of HbA1c levels in female with habitual miso consumption were lower than those of female without. Moreover, habitual miso consumption correlated with average (β = −0.251, p = 0.009), SD (β = −0.175, p = 0.016), and CV (β = −0.185, p = 0.022) of HbA1c levels after adjusting for covariates. However, no association between habitual miso consumption and any glycemic parameters was shown among male. This study clarified the association between habitual miso consumption and good glycemic control, including glycemic variability, in female, but not in male.     

Habitual Miso (Fermented Soybean Paste) Consumption Is Associated with a Low Prevalence of Sarcopenia in Patients with Type 2 Diabetes: A Cross-Sectional Study

Insulin resistance is a risk of sarcopenia, and the presence of sarcopenia is high in patients with type 2 diabetes (T2DM). It has been reported that habitual miso soup consumption was associated with lower insulin resistance. However, the association between habitual miso consumption and the presence of sarcopenia in patients with T2DM, especially sex difference, was unclear. In this cross-sectional study, 192 men and 159 women with T2DM were included. Habitual miso consumption was defined as consuming miso soup regularly. Having both low skeletal muscle mass index (<28.64% for men, <24.12% for women) and low adjusted hand grip strength (<51.26% for men, <35.38% for women) was defined as sarcopenia. The proportions of sarcopenia were 8.7% in men and 22.6% in women. The proportions of habitual miso consumption were 88.0% in men and 83.6% in women. Among women, the presence of sarcopenia was lower in the group with habitual miso consumption (18.8% versus 42.3%, p = 0.018); however, there was no association between habitual miso consumption and the presence of sarcopenia in men. Habitual miso consumption was negatively associated with the presence of sarcopenia in women (adjusted odds ratio (OR), 0.20 (95% confidence interval (CI): 0.06–0.62), p = 0.005) but not in men. This study indicated that habitual miso consumption was associated with the presence of sarcopenia in women but not in men.     

Retrospective Evaluation on the Use of a New Polysaccharide Complex in Managing Paediatric Type 1 Diabetes with Metabolic Syndrome (MetS)

Background: Children and adolescents affected by type 1 diabetes have an increased risk of being overweight or obese and of suffering from cardiometabolic symptoms. Aims: To retrospectively evaluate the effects of a new complex of polysaccharide macromolecules, Policaptil Gel Retard^® (PGR), on auxological and metabolic parameters, glycaemic variability and control parameters in paediatric patients with type 1 diabetes and metabolic syndrome (MetS). Patients and Methods: Data for 27 paediatric patients with a diagnosis of type 1 diabetes in conjunction with obesity and MetS of at least 5 years’ standing were collected and retrospectively studied. Of these, 16 (median age 12.9, range 9.5–15.8 years) had been adjunctively treated with PGR and 11 (median age 12.6, range 9.4–15.6 years) had not been treated with PGR. Auxological, metabolic and glycaemic control and variability parameters and insulin dosing were compared after 6 months in the two groups. Results: PGR significantly reduced BMI standard deviation score (SDS) (p < 0.005), waist SDS (p < 0.005), HbA1c (p < 0.05) and daily mean insulin dose requirement (p < 0.005). A significant improvement was also observed in the metabolic and glycaemic variability parameters of mean daily blood glucose (BG) levels (p < 0.005), SD of daily BG levels (p < 0.0001), mean coefficient of variation (p < 0.05), LBGI (p < 0.0001), HBGI (p < 0.0001), J-index (p < 0.005), total cholesterol (p < 0.005), HDL-cholesterol (p < 0.005) and LDL-cholesterol (p < 0.005) and triglycerides (p < 0.05). Conclusions: PGR produces a good auxological and metabolic response in obese patients with MetS who are affected by type 1 diabetes. It led to a significant reduction in BMI SDS, waist SDS and an improvement in glucose control and variability as well as in other MetS parameters. The use of polysaccharide compounds, especially if associated with appropriate dietary changes, may help achieve treatment targets in type 1 diabetes and reduce the risk that patients develop metabolic syndrome.     

Resemblance of Diet Quality in Families of Youth with Type 1 Diabetes Participating in a Randomized Controlled Behavioral Nutrition Intervention Trial in Boston,MA (2010-2013): A Secondary Data Analysis

Background

Parent–child diet quality resemblance is unknown in families of youth with type 1 diabetes, for whom nutrition is central to disease management.