CIDeRplusGeneral Information:
| Id: | 3,831 |
| Diseases: |
Diabetes mellitus, ketosis-prone
- [OMIM]
Diabetes mellitus, type II - [OMIM] Insulin resistance |
| Homo sapiens | |
| male | |
| article | |
| Reference: | Patel SG et al.(2013) Pathogenesis of A(-)beta(+) ketosis-prone diabetes Diabetes 62: 912-922 [PMID: 23160531] |
Interaction Information:
| Comment | Ketosis-prone diabetes (KPD) subjects had elevated initial HbA1c and fasting plasma glucose levels 4-12 weeks after the index diabetic ketoacidosis (DKA) episode. Characteristically, HbA1c was markedly improved 3-6 months after the index DKA, when the patients were on low doses of insulin or off insulin. Fasting C-peptide was higher in control subjects. The C-peptide/glucose ratio was one-third of the control level in the KPD group. Fasting insulin levels were not different, and Quantitative Insulin Sensitivity Check Index (QUICKI), an index of insulin sensitivity, demonstrated similar levels of insulin resistance in the two groups. |
|
Formal Description Interaction-ID: 38382 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of phenotype |
| Comment | Ketosis-prone diabetes (KPD) subjects had elevated initial HbA1c and fasting plasma glucose levels 4-12 weeks after the index diabetic ketoacidosis (DKA) episode. Characteristically, HbA1c was markedly improved 3-6 months after the index DKA, when the patients were on low doses of insulin or off insulin. Fasting C-peptide was higher in control subjects. The C-peptide/glucose ratio was one-third of the control level in the KPD group. Fasting insulin levels were not different, and Quantitative Insulin Sensitivity Check Index (QUICKI), an index of insulin sensitivity, demonstrated similar levels of insulin resistance in the two groups. |
|
Formal Description Interaction-ID: 38384 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of phenotype |
| Comment | Ketosis-prone diabetes (KPD) subjects had elevated initial HbA1c and fasting plasma glucose levels 4-12 weeks after the index diabetic ketoacidosis (DKA) episode. Characteristically, HbA1c was markedly improved 3-6 months after the index DKA, when the patients were on low doses of insulin or off insulin. Fasting C-peptide was higher in control subjects. The C-peptide/glucose ratio was one-third of the control level in the KPD group. Fasting insulin levels were not different, and Quantitative Insulin Sensitivity Check Index (QUICKI), an index of insulin sensitivity, demonstrated similar levels of insulin resistance in the two groups. |
|
Formal Description Interaction-ID: 38386 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of phenotype decreased circulating C-peptide level |
| Comment | Ketosis-prone diabetes (KPD) subjects had elevated initial HbA1c and fasting plasma glucose levels 4-12 weeks after the index diabetic ketoacidosis (DKA) episode. Characteristically, HbA1c was markedly improved 3-6 months after the index DKA, when the patients were on low doses of insulin or off insulin. Fasting C-peptide was higher in control subjects. The C-peptide/glucose ratio was one-third of the control level in the KPD group. Fasting insulin levels were not different, and Quantitative Insulin Sensitivity Check Index (QUICKI), an index of insulin sensitivity, demonstrated similar levels of insulin resistance in the two groups. |
|
Formal Description Interaction-ID: 38387 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype |
| Comment | Ketosis-prone diabetes (KPD) subjects had elevated initial HbA1c and fasting plasma glucose levels 4-12 weeks after the index diabetic ketoacidosis (DKA) episode. Characteristically, HbA1c was markedly improved 3-6 months after the index DKA, when the patients were on low doses of insulin or off insulin. Fasting C-peptide was higher in control subjects. The C-peptide/glucose ratio was one-third of the control level in the KPD group. Fasting insulin levels were not different, and Quantitative Insulin Sensitivity Check Index (QUICKI), an index of insulin sensitivity, demonstrated similar levels of insulin resistance in the two groups. |
|
Formal Description Interaction-ID: 38389 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype |
| Comment | Triglycerides showed a trend to be higher, and HDL-cholesterol (HDL-C) was 30% lower in KPD. |
|
Formal Description Interaction-ID: 38390 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_activity of |
| Comment | The mean beta-hydroxybutyrate (BOHB) level was twice as high in KPD as in control subjects, but the difference did not attain statistical significance due to individual variability. KPD patients had normal fasting metanephrines and cortisol and normal thyroid, renal, and liver functions. |
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Formal Description Interaction-ID: 38392 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype abnormal fasting metanephrine level |
| Comment | The mean beta-hydroxybutyrate (BOHB) level was twice as high in KPD as in control subjects, but the difference did not attain statistical significance due to individual variability. KPD patients had normal fasting metanephrines and cortisol and normal thyroid, renal, and liver functions. |
|
Formal Description Interaction-ID: 38395 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype abnormal circulating cortisol level |
| Comment | The mean beta-hydroxybutyrate (BOHB) level was twice as high in KPD as in control subjects, but the difference did not attain statistical significance due to individual variability. KPD patients had normal fasting metanephrines and cortisol and normal thyroid, renal, and liver functions. |
|
Formal Description Interaction-ID: 38396 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype |
| Comment | The mean beta-hydroxybutyrate (BOHB) level was twice as high in KPD as in control subjects, but the difference did not attain statistical significance due to individual variability. KPD patients had normal fasting metanephrines and cortisol and normal thyroid, renal, and liver functions. |
|
Formal Description Interaction-ID: 38397 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype |
| Comment | The mean beta-hydroxybutyrate (BOHB) level was twice as high in KPD as in control subjects, but the difference did not attain statistical significance due to individual variability. KPD patients had normal fasting metanephrines and cortisol and normal thyroid, renal, and liver functions. |
|
Formal Description Interaction-ID: 38399 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38400 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound Asparagine/Aspartate |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38407 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound Glutamine/Glutamate |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
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Formal Description Interaction-ID: 38409 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38410 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38411 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38412 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38413 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38414 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_quantity of drug/chemical compound |
| Comment | Asx (Asp/Asn) was 2.3-fold and Glx (Glu/Gln) 4.8-fold higher in the KPD group. Smaller elevations were observed in KPD for glycine (1.4-fold), serine (1.4-fold), alanine (1.2-fold), proline (1.2-fold), and histidine (1.2-fold). Methionine (0.85-fold) and citrulline (0.75-fold) were lower in KPD. |
|
Formal Description Interaction-ID: 38415 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_quantity of drug/chemical compound |
| Comment | To avoid alterations of glutamine and glutamate due to collection methods or storage, five additional, newly diagnosed A-beta+ KPD patients were recruited and their plasma collected using stringent collection and processing methods. The mean glutamine concentration in these new KPD samples was 0.56-fold less than control subjects, and the mean glutamate concentration 1.75-fold more than control subjects. |
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Formal Description Interaction-ID: 38417 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_quantity of drug/chemical compound |
| Comment | To avoid alterations of glutamine and glutamate due to collection methods or storage, five additional, newly diagnosed A-beta+ KPD patients were recruited and their plasma collected using stringent collection and processing methods. The mean glutamine concentration in these new KPD samples was 0.56-fold less than control subjects, and the mean glutamate concentration 1.75-fold more than control subjects. |
|
Formal Description Interaction-ID: 38419 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound |
| Comment | Concentrations of total branched chain amino acids (BCAA) were similar in KPD and control subjects, with no significant differences in valine or isoleucine/leucine. Because MS/MS cannot distinguish isoleucine from leucine, HPLC was used to separate them in samples from 11 KPD patients and 16 control subjects. Leucine and isoleucine concentrations were not different between KPD and control subjects. This was surprising because fasting plasma concentrations of leucine and isoleucine are usually elevated in diabetic patients with imperfect glycemic control. |
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Formal Description Interaction-ID: 38420 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype abnormal circulating branched-chain amino acid level |
| Comment | Concentrations of total branched chain amino acids (BCAA) were similar in KPD and control subjects, with no significant differences in valine or isoleucine/leucine. Because MS/MS cannot distinguish isoleucine from leucine, HPLC was used to separate them in samples from 11 KPD patients and 16 control subjects. Leucine and isoleucine concentrations were not different between KPD and control subjects. This was surprising because fasting plasma concentrations of leucine and isoleucine are usually elevated in diabetic patients with imperfect glycemic control. |
|
Formal Description Interaction-ID: 38446 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Comment | Concentrations of total branched chain amino acids (BCAA) were similar in KPD and control subjects, with no significant differences in valine or isoleucine/leucine. Because MS/MS cannot distinguish isoleucine from leucine, HPLC was used to separate them in samples from 11 KPD patients and 16 control subjects. Leucine and isoleucine concentrations were not different between KPD and control subjects. This was surprising because fasting plasma concentrations of leucine and isoleucine are usually elevated in diabetic patients with imperfect glycemic control. |
|
Formal Description Interaction-ID: 38447 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Comment | Concentrations of total branched chain amino acids (BCAA) were similar in KPD and control subjects, with no significant differences in valine or isoleucine/leucine. Because MS/MS cannot distinguish isoleucine from leucine, HPLC was used to separate them in samples from 11 KPD patients and 16 control subjects. Leucine and isoleucine concentrations were not different between KPD and control subjects. This was surprising because fasting plasma concentrations of leucine and isoleucine are usually elevated in diabetic patients with imperfect glycemic control. |
|
Formal Description Interaction-ID: 38448 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Comment | The catabolic pathways of BCAA through acylcarnitine esters of their distinct ketoacid metabolites were tracked. Isobutyryl-carnitine (C4-AC), from decarboxylation of the valine ketoacid, was 1.5-fold higher in KPD. In contrast, C5-AC, representing acylcarnitine esters of both isovaleryl-CoA and alpha-isomethylbutyryl-CoA (from decarboxylation of the leucine and isoleucine ketoacids, respectively), was 1.3-fold lower in KPD, but tiglyl-carnitine (C5:1-AC), an isoleucine-specific catabolite, was 1.2-fold higher in KPD. In sum, these data indicated that the leucine ketoacid metabolite was decreased in KPD patients. |
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Formal Description Interaction-ID: 38450 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound Isobutyrylcarnitine |
| Comment | The catabolic pathways of BCAA through acylcarnitine esters of their distinct ketoacid metabolites were tracked. Isobutyryl-carnitine (C4-AC), from decarboxylation of the valine ketoacid, was 1.5-fold higher in KPD. In contrast, C5-AC, representing acylcarnitine esters of both isovaleryl-CoA and alpha-isomethylbutyryl-CoA (from decarboxylation of the leucine and isoleucine ketoacids, respectively), was 1.3-fold lower in KPD, but tiglyl-carnitine (C5:1-AC), an isoleucine-specific catabolite, was 1.2-fold higher in KPD. In sum, these data indicated that the leucine ketoacid metabolite was decreased in KPD patients. |
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Formal Description Interaction-ID: 38451 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_quantity of drug/chemical compound Isovalerylcarnitine |
| Comment | The catabolic pathways of BCAA through acylcarnitine esters of their distinct ketoacid metabolites were tracked. Isobutyryl-carnitine (C4-AC), from decarboxylation of the valine ketoacid, was 1.5-fold higher in KPD. In contrast, C5-AC, representing acylcarnitine esters of both isovaleryl-CoA and alpha-isomethylbutyryl-CoA (from decarboxylation of the leucine and isoleucine ketoacids, respectively), was 1.3-fold lower in KPD, but tiglyl-carnitine (C5:1-AC), an isoleucine-specific catabolite, was 1.2-fold higher in KPD. In sum, these data indicated that the leucine ketoacid metabolite was decreased in KPD patients. |
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Formal Description Interaction-ID: 38456 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound Acylcarnitine C5:1 |
| Comment | The confluence of metabolomic and kinetic data indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty acid utilization for energy, leading to accelerated leucine catabolism and transamination of alpha-ketoglutarate to glutamate, with impaired TCA anaplerosis of glutamate carbon. They highlight a novel process of defective energy production and ketosis in A(-)beta(+) KPD. |
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Formal Description Interaction-ID: 38457 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of process |
| Comment | Acetylcarnitine (C2, acylcarnitine ester of acetyl CoA) was lower in KPD, suggesting either decreased production of acetyl CoA or increased shunting of acetyl CoA into oxidative or synthetic pathways. |
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Formal Description Interaction-ID: 38458 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_quantity of drug/chemical compound |
| Comment | Beta-hydroxybutyrylcarnitine (C4-OH), representing intracellular beta-hydroxybutyrate (BOHB), was threefold higher in KPD, suggesting increased ketone synthesis or diminished ketone oxidation. |
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Formal Description Interaction-ID: 38459 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_quantity of drug/chemical compound Hydroxybutyrylcarnitine |
| Comment | Other short-chain acylcarnitines (C4-DC, C5-DC), which include metabolites arising distal to alpha-ketoglutarate in the TCA cycle, such as methylmalonyl/succinyl-carnitine and glutaryl-carnitine, were diminished in KPD. |
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Formal Description Interaction-ID: 38460 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_quantity of drug/chemical compound Methylmalonylcarnitine/Succinylcarnitine |
| Comment | Other short-chain acylcarnitines (C4-DC, C5-DC), which include metabolites arising distal to alpha-ketoglutarate in the TCA cycle, such as methylmalonyl/succinyl-carnitine and glutaryl-carnitine, were diminished in KPD. |
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Formal Description Interaction-ID: 38464 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_quantity of drug/chemical compound Glytarylcarnitine |
| Comment | The molar sum of the seven most abundant fatty acids was similar in KPD and control subjects. Persons consuming American diets have the following rank order of fasting fatty acid concentrations: oleate - palmitate - linoleate; this order was preserved in both groups, and levels of palmitate and oleate were similar, making it unlikely that there were group differences in habitual dietary fat composition. These data suggested that the proclivity for ketosis in KPD patients is not due to excessive fatty acid supply. |
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Formal Description Interaction-ID: 38465 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | The molar sum of the seven most abundant fatty acids was similar in KPD and control subjects. Persons consuming American diets have the following rank order of fasting fatty acid concentrations: oleate - palmitate - linoleate; this order was preserved in both groups, and levels of palmitate and oleate were similar, making it unlikely that there were group differences in habitual dietary fat composition. These data suggested that the proclivity for ketosis in KPD patients is not due to excessive fatty acid supply. |
|
Formal Description Interaction-ID: 38466 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | The molar sum of the seven most abundant fatty acids was similar in KPD and control subjects. Persons consuming American diets have the following rank order of fasting fatty acid concentrations: oleate - palmitate - linoleate; this order was preserved in both groups, and levels of palmitate and oleate were similar, making it unlikely that there were group differences in habitual dietary fat composition. These data suggested that the proclivity for ketosis in KPD patients is not due to excessive fatty acid supply. |
|
Formal Description Interaction-ID: 38467 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | The molar sum of the seven most abundant fatty acids was similar in KPD and control subjects. Persons consuming American diets have the following rank order of fasting fatty acid concentrations: oleate - palmitate - linoleate; this order was preserved in both groups, and levels of palmitate and oleate were similar, making it unlikely that there were group differences in habitual dietary fat composition. These data suggested that the proclivity for ketosis in KPD patients is not due to excessive fatty acid supply. |
|
Formal Description Interaction-ID: 38468 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | The molar sum of the seven most abundant fatty acids was similar in KPD and control subjects. Persons consuming American diets have the following rank order of fasting fatty acid concentrations: oleate - palmitate - linoleate; this order was preserved in both groups, and levels of palmitate and oleate were similar, making it unlikely that there were group differences in habitual dietary fat composition. These data suggested that the proclivity for ketosis in KPD patients is not due to excessive fatty acid supply. |
|
Formal Description Interaction-ID: 38469 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Comment | The molar sum of the seven most abundant fatty acids was similar in KPD and control subjects. Persons consuming American diets have the following rank order of fasting fatty acid concentrations: oleate - palmitate - linoleate; this order was preserved in both groups, and levels of palmitate and oleate were similar, making it unlikely that there were group differences in habitual dietary fat composition. These data suggested that the proclivity for ketosis in KPD patients is not due to excessive fatty acid supply. |
|
Formal Description Interaction-ID: 38471 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | The molar sum of the seven most abundant fatty acids was similar in KPD and control subjects. Persons consuming American diets have the following rank order of fasting fatty acid concentrations: oleate - palmitate - linoleate; this order was preserved in both groups, and levels of palmitate and oleate were similar, making it unlikely that there were group differences in habitual dietary fat composition. These data suggested that the proclivity for ketosis in KPD patients is not due to excessive fatty acid supply. |
|
Formal Description Interaction-ID: 38472 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | Thyroid-stimulating hormone, blood urea nitrogen, creatinine, and aspartate aminotransferase (AST) were normal and similar in both groups. |
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Formal Description Interaction-ID: 38474 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_quantity of complex/PPI Thyroid-stimulating hormone |
| Comment | Thyroid-stimulating hormone, blood urea nitrogen, creatinine, and aspartate aminotransferase (AST) were normal and similar in both groups. |
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Formal Description Interaction-ID: 38484 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype |
| Comment | Thyroid-stimulating hormone, blood urea nitrogen, creatinine, and aspartate aminotransferase (AST) were normal and similar in both groups. |
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Formal Description Interaction-ID: 38496 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of phenotype |
| Comment | Thyroid-stimulating hormone, blood urea nitrogen, creatinine, and aspartate aminotransferase (AST) were normal and similar in both groups. |
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Formal Description Interaction-ID: 38497 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup NOT affects_activity of |
| Comment | Fasting rates of FFA release and acetyl CoA flux are similar in KPD and control subjects. Beta-hydroxybutyrate (BOHB) oxidation and fatty acid disposal are slowed, leading to elevated plasma concentrations of BOHB and FFA. |
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Formal Description Interaction-ID: 38498 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of phenotype |
| Comment | Fasting rates of FFA release and acetyl CoA flux are similar in KPD and control subjects. Beta-hydroxybutyrate (BOHB) oxidation and fatty acid disposal are slowed, leading to elevated plasma concentrations of BOHB and FFA. |
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Formal Description Interaction-ID: 38499 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of |
| Comment | Oxidative decarboxylation of leucine is accelerated in KPD. There was no difference between KPD and control subjects in leucine flux and a trend toward higher valine flux in KPD. The rate of oxidative decarboxylation, or removal of the No 1 carbon of leucine by BCKDH, showed a strong trend to be faster in KPD. Increased BCKDH activity requires increased flux through the earlier BCAT-catalyzed step that drives transfer of NH2 from leucine to alpha-ketoglutarate to generate glutamate. Unless matched by acceleration of the opposing reaction that oxidatively deaminates glutamate to alpha-ketoglutarate, this would promote accumulation of glutamate. |
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Formal Description Interaction-ID: 38500 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of complex/PPI Branched-chain keto acid dehydrogenase complex |
| Comment | Conversion of glutamine to glutamate is accelerated in KPD, without a parallel increase in glutamate carbon oxidation. There was no group difference in glutamine flux, but plasma glutamine concentration trended lower in KPD. The rate of glutamine carbon transfer to glutamate was faster in KPD by several measures: slope of change, absolute synthesis rate of glutamate from glutamine, and fractional synthesis rate of glutamate from glutamine. However, the rate of oxidation of the same glutamate carbon in the TCA cycle was not different between the groups. Thus, increased glutamate production from glutamine in KPD is not matched by a parallel increase in glutamate carbon anaplerosis into the TCA cycle, as predicted from the results of the leucine infusion study. |
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Formal Description Interaction-ID: 38503 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup increases_activity of process glutamine to glutamate conversion |
| Comment | Transfer of amide nitrogen from glutamine to citrulline is slower in KPD. Citrulline flux was slower in KPD than in control subjects, with a trend toward slower transfer of glutamine amide nitrogen to ornithine for citrulline synthesis. |
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Formal Description Interaction-ID: 38504 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_activity of process glutamine to citrulline conversion |
| Comment | The confluence of metabolomic and kinetic data indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty acid utilization for energy, leading to accelerated leucine catabolism and transamination of alpha-ketoglutarate to glutamate, with impaired TCA anaplerosis of glutamate carbon. They highlight a novel process of defective energy production and ketosis in A(-)beta(+) KPD. |
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Formal Description Interaction-ID: 38506 |
disease Diabetes mellitus, ketosis-prone, A- beta+ subgroup decreases_activity of process |