Prealbumin is a small protein which has been widely evaluated as a nutritional and a prognostic marker. The small size and concentration of prealbumin in blood proposes challenges on measuring it with high sensitivity and specificity. Over the years, a number of analytical methodologies have been developed, which may help establish prealbumin as a useful biomarker in routine clinical practice. The aim of the short review was to explore the current literature on the clinical utility of prealbumin and the advances made in the analytical methodologies of prealbumin. We searched MEDLINE, EMBASE and the Cochrane Library for articles published between January 1980 and July 2019, with the general search terms of 'prealbumin', 'prognostic marker', 'nutritional marker', 'analytical methodologies' and 'malnutrition'. Additionally, we selected relevant articles and comprehensive overviews from reference lists of identified studies. The routine use of prealbumin in clinical practice remains debatable; however; it can complement clinical history, anthropometric assessment and physical examination to assess malnutrition with more certainty. Consensus on the clinical applications of prealbumin in the management of malnutrition is warranted.

Transthyretin (TTR) is considered to be associated with insulin resistance in humans. This study aimed to investigate TTR level in gestational diabetes mellitus (GDM) and its association with glucose metabolism.

Fifty pregnant women with GDM and 47 pregnant women with normal glucose tolerance matched for body mass index and age were enrolled in this study. Their blood samples were collected to detect TTR, retinol-binding protein 4 (RBP4), and their association with glucose and lipid metabolism.

Serum TTR levels in the GDM group were significantly higher than those in the control group (median, 93.44 [interquartile range, 73.81, 117.79] μg/ml vs. 80.83 [74.19, 89.38] μg/ml; P = 0.006). GDM subjects had a lower RBP4/TTR ratio than the control subjects (median, 517.57 [interquartile range, 348.38, 685.27] vs. 602.56 [460.28, 730.62]; P = 0.02). The serum TTR concentrations were positively associated with neonatal weight (r = 0.223, P = 0.028), homeostatic model assessment of insulin resistance (r = 0.246, P = 0.015), and fasting blood glucose (FBG) (r = 0.363, P < 0.001). In stepwise multivariate linear regression analysis, FBG (standardized beta = 0.27, P = 0.004) and neonatal weight (standardized beta = 0.345, P < 0.001) were independent predictors of serum TTR concentrations. Additionally, FBG (standardized beta = - 0.306, P = 0.002) and triglyceride (TG) (beta = 0.219, P = 0.025) were independently associated with RBP4/TTR ratio.

Serum TTR concentrations were significantly higher in women with GDM than that in women without GDM, suggesting that elevated TTR level may play a role in the pathogenesis of GDM. Meanwhile, TTR was positively and independently associated with FBG and neonatal weight, while FBG and TG were independent predictors of RBP4/TTR ratio. Moreover, serum TTR levels and RBP4/TTR ratio were considered valuable markers of insulin resistance and GDM.

Zinc is an essential trace element for living organisms and their biological processes. Zinc plays a key role in more than 300 enzymes and it is involved in cell communication, proliferation, differentiation and survival. Zinc plays also a role in regulating the immune system with implications in pathologies where zinc deficiency and inflammation are observed. In order to examine the experimental evidence reported in the literature regarding zinc levels in the body of patients with autoimmune disorders compared to control individuals, a systematic review and meta-analysis were performed. From 26,095 articles identified by literature search, only 179 of them were considered potentially relevant for our study and then examined. Of the 179 articles, only 62 satisfied the inclusion criteria. Particularly for Fixed Model, Zn concentration in both serum (mean effect = -1.19; confidence interval: -1.26 to -1.11) and plasma (mean effect = -3.97; confidence interval: -4.08 to -3.87) samples of autoimmune disease patients was significantly lower than in controls. The data presented in our work, although very heterogeneous in the manner of collecting and investigating samples, have proved to be extremely consistent in witnessing a deficiency of zinc in serum and plasma of patients compared to controls.

Type 1 diabetes mellitus (T1DM) as one of the most well-known autoimmune disease, results from the destruction of β-cells in pancreas by autoimmune process. T1DM is fatal without insulin treatment. The expansion of alternative treatment to insulin is a dream to be fulfilled. Currently autoimmunity is considered as main factor in development of T1DM. So manipulation of the immune system can be considered as alternative treatment to insulin. For the past decades, vitamin A has been implicated as an essential dietary micronutrient in regulator of immune function. Despite major advantage in the knowledge of vitamin A biology, patients who present T1DM are at risk for deficiency in vitamin A and carotenoids. Applying such evidences, vitamin A treatment may be the key approach in preventing T1DM.

Aim. To determine the serum prealbumin (PA), retinol binding protein (RBP), and retinol levels in adult patients with type 1 diabetes (T1D) and to analyze some factors related to those levels. Methods. A total of 93 patients (47 women) were studied. Age, gender, BMI, duration of diabetes, chronic complications, HbA1c, lipid profile, creatinine, albumin, PA, RBP, and retinol were recorded. High and low parameter groups were compared by Mann-Whitney U and χ² tests. Correlation between parameters was analyzed by Spearman's test. Odds of low levels were analyzed by univariate logistic regression and included in the multivariate analysis when significant. Results. 49.5%, 48.4%, and 30.1% of patients displayed serum PA, RBP, and retinol levels below normal values, respectively. A high correlation (Rho > 0.8) between PA, RBP, and retinol serum levels was found. Patients presenting low levels of any of them were predominantly women, normal-weighted, and with lower levels of triglycerides and serum creatinine. No differences in age, macrovascular complications, duration of diabetes, or HbA1c values were observed when comparing low and normal parameter groups. Conclusion. Low serum levels of PA, RBP, and retinol are frequent in T1D adult patients. This alteration is influenced by female sex and serum creatinine and triglyceride levels.

Plasma transthyretin (TTR) is a plasma protein secreted by the liver that circulates bound to retinol-binding protein 4 (RBP4) and its retinol ligand. TTR is the sole plasma protein that reveals from birth to old age evolutionary patterns that are closely superimposable to those of lean body mass (LBM) and thus works as the best surrogate analyte of LBM. Any alteration in energy-to-protein balance impairs the accretion of LBM reserves and causes early depression of TTR production. In acute inflammatory states, cytokines induce urinary leakage of nitrogenous catabolites, deplete LBM stores, and cause an abrupt decrease in TTR and RBP4 concentrations. As a result, thyroxine and retinol ligands are released in free form, creating a second frontline that strengthens that primarily initiated by cytokines. Malnutrition and inflammation thus keep in check TTR and RBP4 secretion by using distinct and unrelated physiologic pathways, but they operate in concert to downregulate LBM stores. The biomarker complex integrates these opposite mechanisms at any time and thereby constitutes an ideally suited tool to determine residual LBM resources still available for metabolic responses, hence predicting outcomes of the most interwoven disease conditions.

Type 1 diabetes is associated with the presence of inflammation, which in turn affects parameters used to assess the vitamin A status. In the present study, we evaluated the influence of inflammatory status on retinol, retinol-binding protein 4 (RBP4), and transthyretin (TTR) in children and adolescents with type 1 diabetes. A total of 40 children with type 1 diabetes (median age, 14.2 y; median BMI-SDS, 0.53; median diabetes duration, 5.8 y; median HbA1c, 7.3%) and 46 healthy subjects (median age, 12.8 y; median BMI-SDS, 0.34; median HbA1c 5.4%) were recruited. Serum levels of CRP were significantly elevated (p = 0.005) and retinol concentrations were significantly lower (p = 0.02) in children and adolescents with type 1 diabetes compared with healthy subjects. Serum RBP4 and TTR showed no differences between the groups. Healthy children with CRP levels above 0.6 mg/L had significant lower levels of retinol (p = 0.03). This was not observed in children with type 1 diabetes. The results suggest that, in contrast to healthy children, minor CRP elevation does not affect vitamin A transport complex in serum of children with type 1 diabetes.

Hypomagnesaemia and hyperleptinemia are common in patients with diabetes. Moreover, it has been demonstrated that leptin stimulates diuresis and natriuresis. The aim of this study was to evaluate the relationship between serum leptin, serum magnesium (Mg) and urinary Mg/urinary creatinine levels in patients with type 1 diabetes.

Serum leptin and Mg and urinary Mg/urinary creatinine levels were measured in 67 patients with diabetes (33 girls and 34 boys). The age, diabetes duration, anthropometric and metabolic parameters of the subjects were matched between girls and boys. The relation of serum leptin levels to serum and urinary Mg/urinary creatinine levels was assessed.

Serum leptin levels of girls with diabetes were higher than those of the boys (14 +/- 5.3 microg/L vs 5.8 +/- 1.5 microg/L, P < 0.001, respectively). The differences for serum Mg and for urinary Mg/urinary creatinine levels were not significant between girls and boys with diabetes. Leptin levels were correlated with urinary Mg/urinary creatinine levels in both girls and boys (r = 0.39, P = 0.02 and r = 0.37, P = 0.03, respectively). In a multivariate regression model, leptin emerged as independent correlates for mean urinary Mg/urinary creatinine in both girls and boys with the total variance explained being 14%, and 15%, respectively.

The data suggest that serum leptin might be related to increased urinary Mg loss in patients with type I diabetes.

Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic beta-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca(2+) channels. TTR also protected against beta-cell apoptosis. The concentration of TTR tetramer was decreased, whereas that of a monomeric form was increased in sera from patients with type 1 diabetes. The monomer was without effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer constitutes a component in normal beta-cell function. Conversion of TTR tetramer to monomer may be involved in the development of beta-cell failure/destruction in type 1 diabetes.

Thirty-four children were followed up prospectively for 5 years from the onset of diabetes regarding serum magnesium, zinc and some proteins. Serum magnesium decreased to significantly lower values (0.76 +/- 0.05 mmol l-1) than those in matched controls after 2 and 5 years, with the lowest mean values in diabetic girls. Serum zinc concentration was higher in the diabetic group than in the control children, and again the diabetic girls differed most from the controls. Serum prealbumin was significantly lower in the diabetic patients after 2 and 5 years than in the controls. Serum albumin was also slightly reduced in the diabetic patients, while orosomucoid was normal. These data indicate chronic magnesium deficiency and insufficient liver synthesis of certain serum proteins in diabetic children.

The clinical characteristics of 60 consecutive children < 16 years in a Swedish county with newly diagnosed diabetes mellitus, are described. Twenty-four of them were 5.0-9.9 years old. The fathers of 12% had diabetes. There was no seasonal variation in the onset of diabetes. Presenting symptoms were polyuria and polydipsia in more than 90% of the cases. School children had a longer duration of symptoms than pre-school children. Most of the children were in a good state of health, and none were unconscious on admission. HbA1C was a good indicator of diabetes duration (R2 = 0.32). Patients with Coxsackie B IgM antibodies had lower blood glucose than those without such detectable antibodies.

The authors, by means of a recently introduced method, evaluated the intraplatelet concentrations of magnesium in 45 normotensive patients with type II diabetes mellitus, in 45 hypertensive diabetics and in 15 healthy controls. They also evaluated plasma and erythrocyte concentrations of the cation through direct current plasma spectrometer. Both normotensive and hypertensive diabetics showed a reduction in plasma, erythrocyte, and platelet concentrations of magnesium compared to controls. On the contrary, no significant difference was found between hypertensive and normotensive diabetics with regard to plasma and erythrocyte magnesium, whereas intraplatelet assay of the ion pointed out significantly lower concentrations of magnesium in hypertensive compared to normotensive patients (56.4 +/- 9.0 vs 60.7 +/- 10.2 micrograms/10(8) cells--p < 0.05). The authors believe that intraplatelet assay of magnesium may be the most reliable method for the evaluation of the cation in hypertensive diabetics, probably because platelets share common features with smooth muscle cells, including the alpha-2-adrenoceptor cyclase system and a coupling mechanism concerning the calcium-dependent contraction.

In order to investigate the relationships between metals zinc [Zn], copper [Cu], magnesium [Mg], or Calcium [Ca] and noninsulin-dependent diabetes mellitus, 65 patients of newly diagnosed noninsulin-dependent diabetes mellitus and 54 nondiabetic healthy controls were studied. The concentrations of selected metals in fasting blood samples and 24-h urine collections were determined. Hyperzincuria and hypermagnesuria were detected in diabetic patients (p < 0.01). The diabetics also had lower Zn and Mg, and higher Cu, and Ca levels in their plasma than those of the controls, but the statistical differences in Ca and Mg were not significant. Significantly lower Zn and higher Ca levels in erythrocytes were found in diabetic patients (p < 0.01). There is evidence of a significant difference in metals status between diabetic patients with or without the specific complications. This study further indicates that patients with NIDDM on Taiwan also have distinct changes in their metals status, and these perturbations are associated with some diabetic complications.

Serum albumin, transferrin, transthyretin (prealbumin), and retinol binding protein concentrations were determined in 74 children with insulin-dependent diabetes mellitus before and after a 10-day camp session during which blood glucose concentrations were controlled. Initial concentrations of albumin and transferrin in the subjects were not different from those in 21 children and adults without diabetes, and did not change during the study period. Transthyretin and retinol binding protein concentrations were lower in subjects with diabetes than in the control population, and increased from 182 +/- 49 mg/l and 42.5 +/- 13.4 mg/l to 232 +/- 71 mg/l and 47.2 +/- 13.5 mg/l, respectively. We observed correlations between the changes in transferrin, transthyretin, and retinol binding protein. Although reductions in glycated albumin and transferrin indicated improvement in blood glucose control, there was no correlation between changes in the glycated markers and the concentrations of serum transport proteins. Thus, serum protein concentrations were influenced by the metabolic control of diabetes, but did not directly reflect blood glucose.

There is accumulating evidence that the changes which occur in the metabolism of some micronutrients in diabetes mellitus might have a specific role in the pathogenesis and complications of this disease. Magnesium deficiency is the most evident disturbance of metal metabolism in insulin-dependent diabetes mellitus. Hypomagnesemia has been linked both to the acute metabolic and late chronic complication of diabetes. Of particular concern, is the association between hypomagnesemia and ischemic heart disease and severe retinopathy in humans with diabetes mellitus. Appropriate magnesium supplementation might prove beneficial in normalizing the low plasma and tissue magnesium levels and prevent or retard the development of vascular complications in diabetic patients. However, well designed and documented experiments need to be performed before the rationales for such therapy are well established.

Platelet aggregation in response to collagen, adenosine diphosphate and arachidonic acid was studied prospectively in 30 children with Type 1 (insulin-dependent) diabetes mellitus. The studies began on admission to hospital and continued throughout the two years following diagnosis. The results were compared with those in 44 health control children. Collagen-induced aggregation was significantly decreased in the diabetic children on admission in comparison to the healthy children. In contrast, the aggregation induced by adenosine diphosphate (1.1 mumols/l, p less than 0.05) and arachidonic acid (0.25 mmol/l, p less than 0.05) was increased on admission. The magnitude of the platelet shape change after adenosine diphosphate stimulation was small at the onset of the disease but was significantly increased towards normal during the two years of follow-up. On admission, the primary wave aggregation induced by adenosine diphosphate was positively and significantly correlated to some of the lipoprotein fractions that were disturbed at that time, especially triglycerides in high-density lipoproteins. After two years of treatment the platelet aggregability in the diabetic children had been restored to normal.