Elevation of serum alkaline phosphatase activity and related enzymes in diabetes mellitus

Goldberg, David M.; Martin, Jennifer V.; Knight, A. H.

doi:10.1016/s0009-9120(77)90116-3

Cited by 46 publications

(16 citation statements)

References 18 publications

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“…However, the reason for ALT causing insulin resistance remains elusive. Observationally, ALP is not clearly associated with T2DM1132, consistent with these results. Observationally, GGT is also usually positively associated with diabetes34, even using methods that enable correlated exposures, such as liver enzymes to be disentangled4.…”

Section: Discussionsupporting

confidence: 83%

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Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

Liu

Yeung

Lin

et al. 2016

Sci Rep

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We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT was associated with higher risk of diabetes, odds ratio (OR) 2.99 per 100% change in concentration (95% confidence interval (CI) 1.62 to 5.52) but ALP OR 0.92 (95% CI 0.71 to 1.19) and GGT OR 0.88 (95% CI 0.75 to 1.04) were not. Genetically predicted ALT, ALP and GGT were not clearly associated with CAD/MI (ALT OR 0.74, 95% CI 0.54 to 1.01, ALP OR 0.86, 95% CI 0.64 to 1.16 and GGT OR 1.08, 95% CI 0.97 to 1.19). We confirm observations of ALT increasing the risk of diabetes, but cannot exclude the possibility that higher ALT may protect against CAD/MI. We also cannot exclude the possibility that GGT increases the risk of CAD/MI and reduces the risk of diabetes. Informative explanations for these potentially contradictory associations should be sought.

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Section: Discussionsupporting

confidence: 83%

“…MR takes advantage of the random allocation of genetic endowment at conception to provide randomization analogous to the randomization in randomized controlled trials1011 and is an increasingly popular means of obtaining un-confounded estimates. No previous MR study has examined the role of liver enzymes in CVD and T2DM.…”

mentioning

confidence: 99%

Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

Liu

Yeung

Lin

et al. 2016

Sci Rep

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“…Grown MSCs from STZ animals revealed an increased ALP activity and an impaired collagen production at late culture time points. Increased ALP activity was previously described in osteoblastic cells grown in vitro, in chronic hyperglycemic conditions [Balint et al, ; Botolin and McCabe, ], and in the serum of diabetic patients [Goldberg et al, ; Massé et al, ]. Nonetheless, it has been suggested that ALP within the diabetic environment presents an altered kinetic profile, supposedly in a process related to changes in metal‐binding properties [Rezende et al, ; Fernandes et al, ].…”

Section: Discussionmentioning

confidence: 96%

The Osteogenic Priming of Mesenchymal Stem Cells is Impaired in Experimental Diabetes

Silva

Sampaio

Fernandes

et al. 2015

J of Cellular Biochemistry

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Diabetes mellitus encompasses a group of metabolic conditions embracing the dysfunction and failure of various tissues and organs, including bone. Sustained bone alterations seem to result from anabolic, rather than catabolic processes, and suggest a decreased osteoblastic recruitment and activity. Current knowledge on the cellular and molecular mechanisms were provided by studies performed with osteogenic populations cultured in diabetic-simulated conditions, and osteogenic-induced precursor populations harvested from diabetic animals, sustaining an impaired cellular behavior in terms of osteogenic responsiveness and function. However, the reasons leaning to this impairment remain essentially unknown, as the priming capability and functionality of undifferentiated precursors, developed within the diabetic environment, have not been addressed. Accordingly, this work aims to evaluate the functionality and osteogenic priming capability of bone marrow-derived mesenchymal stem cells (MSCs), harvested from animals with experimental diabetes, and grown in the absence of any given differentiation factor. MSCs developed within a diabetic microenvironment displayed an impaired behavior, with diminished cell viability and proliferation, altered cytoskeleton organization, impaired osteogenic priming, and increased adipogenic activation. Further, the osteogenic induction of diabetic MSCs resulted in an impaired osteogenic commitment. The modified cell phenotype may be related, at least in part, with altered activity of ERK WNT and p38 signaling pathways in diabetic-derived cultures. Specific strategies, aiming the modulation of the verified hindrances, may be of therapeutic value to enhance the functionality of diabetic MSCs and sustain an improved outcome in the metabolism and regeneration of the bone tissue in diabetic conditions.

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“…7 Disturbances in liver function tests (LFT) are well recognized in some diabetic patients, 8 " 13 especially in acute metabolic decompensation. 1415 However, in diabetic patients, the prevalence of abnormal LFT results and their relationships to clinical findings and diabetes per se, as well as to pathologic changes in liver structure, are controvers i a l«..l, [15][16][17][18] In this study, the prevalence of abnormal LFT results and their relationships to clinical findings were assessed using multivariate analysis in an unselected population of diabetic outpatients. In addition, the reliability of common LFTs in assessing histologic changes in the liver was analyzed in hospitalized diabetic patients undergoing diagnostic liver biopsy.…”

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confidence: 99%

Liver Function Tests in Diabetic Patients

Salmela

Sotaniemi

Niemi³

et al. 1984

Diabetes Care

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Nine different liver function tests (LFT) were assessed in 175 unselected diabetic outpatients stabilized on diet, insulin, or oral hypoglycemic drugs. In another group of 72 diabetic inpatients having diagnostic liver biopsy, relationships between LFT and histologic changes in the liver were investigated. Abnormalities in at least one of the tests were noted in 57% of the outpatients, and two tests gave pathologic results in 27%. The non-insulin-dependent diabetic patients more often had abnormal LFT results than did the insulin-dependent diabetic patients. Serum chenodeoxycholic acid concentrations were increased in 27%, gamma-glutamyl transpeptidase (gGT) activities in 19%, and alanine aminotransferase (Alt) activities in 17% of the outpatients, but the increases were rarely more than twice the upper limit of normal. In multivariate analysis, outpatients who were overweight, showed poor diabetes control during a short duration of diabetes controlled by treatment with diet or oral agents, and had a mature age at onset of diabetes displayed the most significant clinical explanatory variables associated with abnormal Alt. In the inpatients, the percentages of abnormal Alt and gGT results were augmented, along with increasing severity of histologic changes, but the mean values of Alt and gGT did not differ significantly between the various histologic groups. In addition, the diabetic patients with nonspecific inflammatory changes or increase in liver fibrosis often showed normal or only minor elevations in these test values.

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Elevation of serum alkaline phosphatase activity and related enzymes in diabetes mellitus

Cited by 46 publications

References 18 publications

Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

The Osteogenic Priming of Mesenchymal Stem Cells is Impaired in Experimental Diabetes

Liver Function Tests in Diabetic Patients

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