Serum Alkaline Phosphatase Pdf
The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.
Serum Alkaline Phosphatase Pdf
This study was motivated by the limited and inconclusive evidence regarding the ALP levels and incident diabetes, and a special opportunity to address this question in a large, randomized controlled trial with regular antihypertensive treatments, BP measurements and diabetes status reports. Specifically, using data from China Stroke Primary Prevention Trial (CSPPT) , we aimed to investigate the prospective association between serum ALP and new-onset diabetes among hypertensive adults, and to examine possible modifiers on the association.
We first explored the association between serum ALP and new-onset diabetes using thin plate regression splines in generalized additive models implemented by the R package mgcv. Then multivariable logistic regression models [odds ratio (OR) and 95% confidence interval (CI)] were used to evaluate relation of serum ALP with new-onset diabetes and new-onset IFG, without and with adjustment for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, FG, total cholesterol (TC), triglycerides (TG), eGFR, folate, tHcy and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period. As additional exploratory analyses, possible modifications on the association between serum ALP and new-onset diabetes were also evaluated by stratified analyses and interaction testing.
Baseline characteristics of participants by baseline ALP quartiles are presented in Table 1. The mean and median serum ALP levels were 100 IU/L (SD, 30.5) and 96 IU/L, respectively. Participants with higher ALP levels were older and more likely to be female; had higher SBP, TG, high-density lipoprotein (HDL) cholesterol, FG, folate levels at baseline and time-averaged on-treatment SBP during the treatment period; lower BMI, DBP, TC, tHcy levels at baseline and time-averaged on-treatment DBP during the treatment period; and lower frequency in use of antihypertensive drugs and antiplatelet drugs at baseline, as wells as lower frequency of current smoking, alcohol drinking and family history of diabetes (Table 1).
The association between baseline serum alkaline phosphatase (ALP) and change in FG levels. Adjusted for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, fasting glucose (FG), total cholesterol (TC), triglycerides (TG), eGFR, folate, total homocysteine and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period. The analysis was only included subjects without physician-diagnosed diabetes, or use of glucose-lowering drugs during follow-up
In order to further examine the association between serum ALP and new-onset diabetes, we investigated the relation of change in ALP with new-onset diabetes. We categorized the participants into four groups according to median of baseline serum ALP (96 IU/L): persistently low ALP levels (
The association between baseline serum alkaline phosphatase (ALP, per SD increment) and new-onset diabetes in various groups. Adjusted for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, fasting glucose (FG), total cholesterol (TC), triglycerides (TG), eGFR, folate, total homocysteine and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period, if not be stratified
Our study demonstrated that there was a positive association between baseline serum ALP levels and new-onset diabetes, independent of other liver aminotransferases, treated BP and other important confounders, among hypertensive patients. Moreover, our study expanded the results of previous studies by demonstrating that the positive association between baseline serum ALP levels and new-onset diabetes was more pronounced in participants with lower tHcy or higher FG levels.
Second, our results showed that tHcy and FG levels significantly modified the association between serum ALP and the risk of new-onset diabetes. A stronger association was found in those with lower tHcy (
In summary, higher serum ALP was significantly associated with increased risk of new-onset diabetes among hypertensive patients, especially in those with lower tHcy or higher FG levels. If further confirmed, our findings support the strategy to identify and modulate diabetes risk in hypertensive patients by measuring and optimizing individual serum ALP levels.
Alkaline phosphatases are a group of isoenzymes, located on the outer layer of the cell membrane; they catalyze the hydrolysis of organic phosphate esters present in the extracellular space. Zinc and magnesium are important co-factors of this enzyme. Although alkaline phosphatases are present in different body tissues and have different physiochemical properties, they are true isoenzymes because they catalyze the same reaction. In the liver, alkaline phosphatase is cytosolic and present in the canalicular membrane of the hepatocyte. Alkaline phosphatase is present in decreasing concentrations in the placenta, ileal mucosa, kidney, bone, and liver. The majority of alkaline phosphatase in serum (more than 80%) is released from the liver and bone, and in small amounts from the intestine. Even though alkaline phosphatases are present in many tissues throughout the body, their precise physiological function remains largely unknown.
Alkaline phosphatases are classified as tissue-specific and tissue-nonspecific types. Alkaline phosphatases found in the intestine, placenta, and germinal tissue are tissue-specific. This means they are found only in the tissues where they are expressed in physiological conditions. They may also contribute to the circulating pool of serum alkaline phosphatase under specific situations when there is increased stimulation of their production. The tissue-nonspecific alkaline phosphatases form most of the fraction circulating in serum and, therefore, are of clinical interest. A single gene encodes it and is expressed in the liver, bone, and kidneys. Intestinal alkaline phosphatase is coded by a separate gene, which is different from the gene that codes for placental alkaline phosphatase and the Regan isoenzyme (produced in excess amounts in Hodgkin lymphoma). All tissue-nonspecific alkaline phosphatases have the same amino acid sequence but different carbohydrate and lipid side chains; post-translational modifications confer their unique physicochemical properties.
Serum alkaline phosphatase levels will vary with age in normal individuals. Levels are high during childhood and puberty due to bone growth and development. The decrease in level in the 15 to the 50-year age group is slightly higher in men than in women. These levels rise again in old age (significant difference in gender distribution). The reasons for these normal variations are not known. Research has shown a positive correlation between body weight and smoking, and there is an inverse correlation with height.
In healthy individuals, the circulating enzyme is primarily derived from the liver and bone. In some individuals, this enzyme comes from the intestinal tract to a minimal extent. In individuals with blood groups O and B, serum alkaline phosphatase levels increase after consuming a fatty meal, due to contribution from the intestinal tract. As this elevation can persist for up to 12 hours in the serum, the recommendation is to check the serum enzyme levels in a fasting state.
The human alkaline phosphatases (hALP) are found anchored on the cell membrane by glycosylphosphatidylinositol. They are released in the serum by the action of specific phospholipase. It has a half-life of 7 days, and clearance from serum is independent of bile duct patency or functional capacity of the liver. However, the site of degradation of alkaline phosphatase is not known. Serum alkaline phosphatase levels may remain elevated for up to 1 week after the resolution of biliary obstruction. The liver is the source in most patients with elevated enzyme levels. Increased osteoblast activity seen in disorders of the bone or normally during periods of growth is the next likely contributor. The influx of placental alkaline phosphatase in the late third trimester contributes to the rise in pregnant women.
The mechanism of the increase in alkaline phosphatase in hepatobiliary disorders has been a matter of debate. Research has convincingly shown that it is due to increased enzyme synthesis and not to reduced hepatobiliary excretion of the enzyme. Increased hepatic enzyme activity demonstrably parallels the rise in serum alkaline phosphatase activity; this occurs primarily due to increased translation of the mRNA of alkaline phosphatase (mediated by the rising bile acid concentration) and increased secretion of alkaline phosphatase into serum via canalicular leakage into the hepatic sinusoid. The mechanism that precipitates its release into circulation has not been elucidated. Studies report that vesicles containing alkaline phosphatase, and many such enzymes bound to the sinusoidal membranes, are found in the serum of patients with cholestasis. Because alkaline phosphatase is newly synthesized in response to biliary obstruction, its serum level may be normal in the early phase of acute biliary obstruction even when the serum aminotransferases are already at their peak.
Blood should be drawn after a fast of at least 8 hours. Serum and heparinized plasma give the same results. Slight hemolysis is tolerable, but gross hemolysis should be avoided. Certain sample storage conditions tend to increase serum ALP. There is a significant increase in activity after the warming of previously refrigerated or frozen sera. The ALP activity in fresh serum increases by up to 2% in 6 hours at 25C. Increases of up to 30% of ALP activity occur after the frozen serum is thawed and in lyophilized specimens after reconstitution. These increases may be due to the release of ALP from complexes with lipoproteins or because the non-complexed enzyme has greater activity. It is best to analyze ALP specimens the same day they are drawn. The specimen can be drawn either in a plain red-top tube or a speckled-red-top tube with gel as a serum separator, employing normal phlebotomy procedures. To avoid contamination, do not draw tubes containing anticoagulants before the red-top/speckled-red-top tube.