WO2017161105A1 - Procédés de traitement d'une altération de la tolérance au glucose et/ou d'une réduction de la sécrétion d'insuline - Google Patents
Procédés de traitement d'une altération de la tolérance au glucose et/ou d'une réduction de la sécrétion d'insuline Download PDFInfo
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- WO2017161105A1 WO2017161105A1 PCT/US2017/022680 US2017022680W WO2017161105A1 WO 2017161105 A1 WO2017161105 A1 WO 2017161105A1 US 2017022680 W US2017022680 W US 2017022680W WO 2017161105 A1 WO2017161105 A1 WO 2017161105A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
- G01N33/721—Haemoglobin
- G01N33/723—Glycosylated haemoglobin
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
- G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/50—Determining the risk of developing a disease
Definitions
- the present disclosure relates to methods of treating impaired glucose tolerance and/or decreased insulin secretion in a subject.
- Adiponectin is an adipocyte-secreted hormone that acts on multiple tissues to enhance insulin action, lipid utilization, and endothelial function. Adiponectin concentrations vary by more than 25-fold among healthy individuals. While low adiponectin strongly predicts diabetes, cardiovascular disease, and death, little is known about effects of very high adiponectin concentrations.
- the present disclosure provides methods of treating impaired glucose tolerance and/or decreased insulin secretion in a subject.
- the present disclosure provides a method of treating or preventing diabetes in a subject, the method comprising determining a baseline level of adiponectin in a sample of the subject; and initiating a therapeutic regimen for the subject if the baseline level of adiponectin is at least about 49 pg/mL.
- the present disclosure provides a method of preventing insulin resistance in a subject having a normal HOMA-IR level, the method comprising identifying the subject as having a normal HOMA-IR level; determining an adiponectin level in a sample of the subject; and initiating a therapeutic regimen for the subject if the adiponectin level is less than 10 pg/mL.
- the present disclosure provides a method of identifying a subject as being at elevated risk for developing diabetes, the method comprising determining a level of adiponectin of at least 49 mg/mL in a sample associated with the subject and identifying the subject as being at elevated risk for developing diabetes based at least in part on the level of adiponectin in the sample.
- the present disclosure provides a method of identifying a subject as being at elevated risk for developing coronary artery disease (CAD), the method comprising obtaining a level of adiponectin in a biological sample associated with the subject; obtaining an age of the subject; and identifying the subject as being at elevated risk for developing CAD if a mathematical transformation (e.g., a logarithmic transformation) of the adiponectin level falls below a predetermined threshold.
- a mathematical transformation e.g., a logarithmic transformation
- the present disclosure provides a method of treating or preventing metabolic disease in a subject, the method comprising determining an elevated level of adiponectin associated with the subject and thereafter initiating a therapeutic regimen in the subject to affect a decrease in the adiponectin level associated with the subject.
- FIG. 1 shows a ROC contrast plot with comparative AUC values for several predictive diabetes models consistent with the present disclosure in comparison to several predictive diabetes models that do not consider adiponectin levels.
- FIG. 2 illustrates that adiponectin levels and LP-IR scores are inversely correlated, suggesting that low adiponectin levels may be associated with a dyslipoproteinemia component of metabolic disease.
- FIG. 3 is a dendogram showing divisive clustering of various biomarkers using principal components, with four specific correlations (ln[eAG] and ln[A1 c]; Infinsulin] and ln[HOMA-IR]; In [leptin-BMI] and ln[leptin]; and ln[QA] and ln[FFA]) showing very strong correlations (r>0.90).
- FIG. 4 shows a heat map for absolute value of Pearson's Correlation between biomarkers and cluster component scores (N ⁇ 1 ,500); lighter shading indicates areas of high correlation values (approaching 1 ) while darker shading indicates areas of relatively low correlation (approaching 0).
- FIG. 5 illustrates that testing the 415 subjects of Example 1 with HOMA-IR (Glucose (in mg/dl_) * lnsulin/405) alone would have resulted in a 33% misdiagnosis rate of subjects with signs of insulin resistance. In contrast, diagnosis using adiponectin accurately identified this subset of subjects with signs of insulin resistance but normal HOMA-IR values.
- FIG. 6 shows results of an OGTT test in subjects with discordant adiponectin (e.g., low adiponectin) compared to HOMA-IR.
- the plot on the top shows glucose response curves, while the plot on the bottom shows insulin response curves, for subjects with discordant (low) adiponectin levels and normal HOMA-IR (dashed line) compared subjects with normal adiponectin levels and normal HOMA-IR (solid line).
- FIG. 7 shows characteristics of subjects having very high adiponectin levels (at least 50 pg/mL) compared to subjects having adiponectin levels of less than 50 pg/mL.
- FIG. 8 shows that subjects with very high adiponectin levels (at least 50 pg/mL) are more glucose intolerant (top panel) but have lower fasting insulin levels and impaired insulin response to an oral glucose load (bottom panel) compared to subjects having adiponectin levels less than 50 pg/mL.
- FIG. 9 shows ROC curves for subjects with very high adiponectin levels (at least 50 pg/mL) using (1 ) a base model including age, gender and BMI; (2) a HOMA-IR model; (3) the Japan IR model (log[lnsulin * Glucose/Adiponectin]); and (4) an OGTT Index model.
- a base model including age, gender and BMI
- a HOMA-IR model the Japan IR model (log[lnsulin * Glucose/Adiponectin])
- OGTT Index model an OGTT Index model.
- Each of the HOMA-IR, Japan IR, and OGTT Index models perform significantly better than the base model for this subset of subjects with very high adiponectin levels.
- FIG. 10 demonstrates that ROC curves derived from the Japan index (log[lnsulin * Glucose/Adiponectin]) and the HOMA-IR model (Glucose (in mg/dl_) * lnsulin/405) were not significantly different in predicting IGT in the subjects studied in Example 1 .
- FIG. 1 1 shows probability of coronary artery disease (CAD) based on a bivariate effect of age and log[Adiponectin] in 18 test subjects (light circles) and 16 control subjects (dark circles).
- CAD coronary artery disease
- adiponectin has been associated with type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), atherogenic lipid profiles, and essential hypertension. Studies have demonstrated that adiponectin has diagnostic and prognostic values as a biomarker of obesity, insulin sensitivity, and CVD.
- Adiponectin is produced almost exclusively by adipose tissue. Circulating monomers assemble to form trimers, hexamers, high-molecular weight (HMW) oligomers, and other multimeric forms. Adiponectin exerts insulin-sensitizing, anti-inflammatory and anti-apoptotic actions on a variety of cell types. Metabolically unfavorable conditions tend to downregulate adiponectin secretion, which generally causes a reduction in its blood levels.
- an adiponectin level less than 3.9 pg/mL (men) or less than 6.01 pg/mL (women) was the strongest predictor of diabetes among subjects having stage 2 prediabetes based on impaired fasting glucose (IFG) levels.
- An adiponectin level of less than 6.01 g/mL also predicted diabetes among women having stage 1 or stage 2 prediabetes in the same study.
- the present technology is based on the surprising discovery that subjects with high adiponectin levels exhibited enhanced insulin sensitivity, but a greater glucose excursion and decreased insulin response during OGTT, compared to subjects with normal adiponectin levels.
- the present disclosure provides a method of treating or preventing diabetes in a subject, the method comprising determining a baseline level of adiponectin in a sample of the subject; and initiating a therapeutic regimen for the subject if the baseline level of adiponectin is at least about 49 pg/mL.
- the therapeutic regimen comprises a change in diet.
- the therapeutic regimen comprises an increase in exercise.
- the therapeutic regimen comprises administering a composition comprising an omega-3 fatty acid to the subject.
- the therapeutic regimen comprises administering conjugated linoleic acid to the subject.
- the therapeutic regimen comprises administering an adiponectin agonist to the subject.
- the method further comprises determining a baseline HOMA-IR level associated with the subject before the step of initiating the therapeutic regimen. In some embodiments, the baseline HOMA-IR level indicates the subject is normoglycemic. In some embodiments, the method further comprises determining a baseline leptin level in the sample of the subject before the step of initiating the therapeutic regimen. In some embodiments, the baseline leptin level is below a normal leptin level associated with a normoglycemic subject of the same gender as the subject. In some embodiments, the method further comprises determining a baseline apolipoprotein B level in the sample of the subject before the step of initiating the therapeutic regimen.
- the baseline apolipoprotein B level is within a normal apolipoprotein B range associated with normoglycemic subjects of the same gender as the subject.
- the method further comprises determining a baseline LDL-C level in the sample of the subject before the step of initiating the therapeutic regimen.
- the baseline LDL-C level is within a normal LDL-C range associated with normoglycemic subjects of the same gender as the subject.
- the method further comprises determining a baseline LDL- P level in the sample of the subject before the step of initiating the therapeutic regimen.
- the baseline LDL-P level is within a normal LDL-P range associated with normoglycemic subjects of the same gender as the subject.
- the method further comprises determining a baseline HDL-C level in the sample of the subject before the step of initiating the therapeutic regimen. In some embodiments, the baseline HDL-C level is within a normal HDL-C range associated with normoglycemic subjects of the same gender as the subject. In some embodiments, the method further comprises determining a baseline HbA1 c level in the sample of the subject before the step of initiating the therapeutic regimen. In some embodiments, the baseline HbA1 c level is within a normal HbA1 c range associated with normoglycemic subjects of the same gender as the subject. In some embodiments, the method further comprises determining a baseline fasting glucose level in the sample of the subject before the step of initiating the therapeutic regimen.
- the baseline fasting glucose level is within a normal fasting glucose range associated with normoglycemic subjects of the same gender as the subject.
- the method further comprises determining a baseline NT-proBNP level in the sample of the subject before the step of initiating the therapeutic regimen.
- the baseline NT-proBNP level is greater than a normal NT-proBNP range associated with normoglycemic subjects of the same gender as the subject.
- the method further comprises determining a second level of adiponectin in a sample of the subject obtained after the step of initiating the therapeutic regimen.
- the method further comprises discontinuing the therapeutic regimen if the second level of adiponectin is less than 49 pg/mL.
- the sample of the subject is a blood sample.
- the present disclosure provides a method of preventing insulin resistance in a subject having a normal HOMA-IR level, the method comprising identifying the subject as having a normal HOMA-IR level; determining an adiponectin level in a sample of the subject; and initiating a therapeutic regimen for the subject if the adiponectin level is less than 10 pg/mL.
- the therapeutic regimen comprises a change in diet.
- the therapeutic regimen comprises an increase in exercise.
- the therapeutic regimen comprises administering a composition comprising an omega-3 fatty acid to the subject.
- the therapeutic regimen comprises administering conjugated linoleic acid to the subject.
- the therapeutic regimen comprises administering an adiponectin agonist to the subject.
- the method further comprises determining an OGTT result associated with the subject before the step of initiating the therapeutic regimen.
- the OGTT result indicates glucose intolerance and/or impaired insulin response.
- the OGTT comprises administering a 75g oral glucose load to the subject.
- the sample of the subject is a blood sample.
- the present disclosure provides a method of identifying a subject as being at elevated risk for developing diabetes, the method comprising determining a level of adiponectin of at least 49 mg/ml_ in a sample associated with the subject; and identifying the subject as being at elevated risk for developing diabetes based at least in part on the level of adiponectin in the sample.
- the step of identifying comprises identifying the subject as being at elevated risk for developing diabetes based on the level of adiponectin, a fasting insulin level, and a fasting glucose level in the sample, and an age, gender and BMI of the subject.
- the step of identifying comprises determining a ratio of a multiple of the fasting insulin level with the fasting glucose level to the level of adiponectin in the sample. In some embodiments, the step of identifying comprises identifying the subject as being at elevated risk for developing diabetes based at least in part on a ratio of leptin to the level of adiponectin in the sample. In some embodiments, the step of identifying comprises identifying the subject as being at elevated risk for developing diabetes based on the level of adiponectin in the sample but not based on an age, gender or BMI of the subject. In some embodiments, the step of identifying comprises determining a logarithmic transformation of at least the level of adiponectin in the sample.
- the present disclosure provides a method of identifying a subject as being at elevated risk for developing coronary artery disease (CAD), the method comprising obtaining a level of adiponectin in a biological sample associated with the subject; obtaining an age of the subject; and identifying the subject as being at elevated risk for developing CAD if a mathematical transformation of the adiponectin level falls below a predetermined threshold.
- the mathematical transformation comprises a logarithmic transformation.
- the mathematical transformation does not include adjusting the adiponectin level based on an age of the subject.
- the mathematical transformation does not include adjusting the adiponectin level based on a gender of the subject.
- the mathematical transformation does not include adjusting the adiponectin level based on an HDL-C level of the subject. In some embodiments, the mathematical transformation does not include adjusting the adiponectin level based on level of small dense low density lipoprotein (sdLDL) of the subject. In some embodiments, the mathematical transformation does not include adjusting the adiponectin level based on an LDL level of the subject. In some embodiments, the mathematical transformation does not include adjusting the adiponectin level based on a cystatin C level of the subject. In some embodiments, the cystatin C level of the subject is a log[cystatin C] level.
- sdLDL small dense low density lipoprotein
- the mathematical transformation does not include adjusting the adiponectin level based on a cholestanol level of the subject. In some embodiments, the mathematical transformation does not include adjusting the adiponectin level based on an HDL ApoE level of the subject. In some embodiments, the mathematical transformation does not include adjusting the adiponectin level based on an insulin level of the subject.
- the present disclosure provides a method of treating or preventing metabolic disease in a subject, the method comprising determining an elevated level of adiponectin associated with the subject; and thereafter initiating a therapeutic regimen in the subject to affect a decrease in the adiponectin level associated with the subject.
- the elevated level of adiponectin associated with the subject is at least 50 pg/mL.
- the therapeutic regimen comprises administering to the subject one or more n-3 polyunsaturated fatty acids (n-3 PUFAs).
- the therapeutic regimen comprises administering to the subject conjugated linoleic acids (CLA).
- the high adiponectin group exhibited enhanced insulin sensitivity but a greater glucose excursion and decreased insulin response during OGTT as compared to the normal group (p ⁇ 0.05). Ferritin did not differ.
- HDL OGTT parameters a combination of adiponectin, free fatty acids, a-hydroxybutyrate, ferritin, LGPC and C-peptide
- adiponectin a combination of adiponectin, free fatty acids, a-hydroxybutyrate, ferritin, LGPC and C-peptide
- Removing adiponectin from the HDL OGTT parameters was insignificant (AUC 0.804 vs. 0.795).
- Use of adiponectin alone or leptin:adiponectin ratio alone were each less predictive (AUC values of 0.702 and 0.716, respectively) than HOMA-IR.
- adiponectin and LP-IR Score may be viewed as forming their own dimension in a cluster analysis. This implies from a latent variable point of view that both adiponectin and LR-IR are manifested from the same underlying physiology.
- each disjoint cluster includes a cluster component score based on a linear combination of the weighted, standardized biomarker values contained within that cluster.
- Principal component (pc) analysis that maximized the amount of explained variability yielded linear combinations.; disjoint clusters are correlated because the principal components were rotated (i.e., not orthogonal).
- the number of clusters was determined by considering several factors, including eigenvalues, minimum R-squared value between a biomarker and its cluster component score, total variability explained in the data, and subject matter knowledge.
- FIG. 6 shows glucose response and insulin response curves for the subset of subjects with normal HOMA-IR scores.
- the subset of subjects with discordant low adiponectin ( ⁇ 10 mg/L) show signs of glucose intolerance compared to the subset of subjects with normal adiponectin levels (at least 10 mg/L) after a 75g oral glucose load.
- the bottom panel shows that the discordant subjects showed signs of impaired insulin response compared to the subset of subjects with normal adiponectin levels after the 75g oral glucose load.
- FIG. 8 shows glucose response and insulin response curves for the subjects with very high adiponectin levels (at least 50 pg/mL; median 99.0 pg/mL). These subjects tended to be more glucose intolerant (top panel) but had lower fasting insulin levels and impaired insulin response (bottom panel) to an oral glucose load compared to the subjects with normal or low adiponectin levels.
- ROC curves for the subjects with adiponectin levels below 50 pg/mL are shown in FIG. 9.
- models including HOMA-IR (ref. no. 20); a combination of Insulin, Glucose and Adiponectin (ref. no. 30); or the combination of adiponectin, free fatty acids, a- hydroxybutyrate, ferritin, LGPC and C-peptide (i.e., "HDL OGTT-lndex"; ref. no. 40) to the base model (age, gender and BMI; ref. no. 10) each significantly improved IGT prediction.
- Specific increases for each improved model are shown in Table 4 below.
- FIG. 10 shows a comparison of the Japan IR Index model (Log[lnsulin * Glucose/Adiponectin]; ref. no. 30) with the HOMA-IR model (ref. no. 20) and a base model including age, gender and BMI (ref. no. 10).
- the Japan IR Index model accounted for 2% more variability than the HOMA-IR model in predicting IGT.
- that improvement was not statistically significant, as shown in Table 5 below. Table 5.
- CAD coronary artery disease
- HDL-cholesterol HDL-C
- homocysteine Log[Homocysteine]
- adiponectin Log[Adiponectin]
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Abstract
La présente invention concerne des procédés de diagnostic, de traitement et/ou de prévention d'une altération de la tolérance au glucose et/ou d'une réduction de la sécrétion d'insuline chez un sujet.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7592180B2 (en) * | 2004-09-28 | 2009-09-22 | Otsuka Pharmaceutical Co., Ltd. | Method for evaluating insulin resistance |
WO2010103585A1 (fr) * | 2009-03-08 | 2010-09-16 | Yokota Mitsuhiro | Procédé pour évaluer un syndrome métabolique ou une maladie associée à celui-ci |
US20150193587A1 (en) * | 2005-10-11 | 2015-07-09 | Health Diagnostic Laboratory, Inc. | Diabetes-related biomarkers and methods of use thereof |
US20150219639A1 (en) * | 2008-07-17 | 2015-08-06 | Ikfe Institut Fur Klinische Forschung Und Entwicklung Gmbh | Method of Treating a Subject According to Biomarkers for Insulin Resistance |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7592180B2 (en) * | 2004-09-28 | 2009-09-22 | Otsuka Pharmaceutical Co., Ltd. | Method for evaluating insulin resistance |
US20150193587A1 (en) * | 2005-10-11 | 2015-07-09 | Health Diagnostic Laboratory, Inc. | Diabetes-related biomarkers and methods of use thereof |
US20150219639A1 (en) * | 2008-07-17 | 2015-08-06 | Ikfe Institut Fur Klinische Forschung Und Entwicklung Gmbh | Method of Treating a Subject According to Biomarkers for Insulin Resistance |
WO2010103585A1 (fr) * | 2009-03-08 | 2010-09-16 | Yokota Mitsuhiro | Procédé pour évaluer un syndrome métabolique ou une maladie associée à celui-ci |
Non-Patent Citations (4)
Title |
---|
ALEIDI, S ET AL.: "Adiponectin Serum Levels Correlate with Insulin Resistance in Type 2 Diabetic Patients", SAUDI PHARMACEUTICAL JOURNAL, vol. 23, 2015, pages 250 - 256, XP055423532 * |
FISMAN, EZ ET AL.: "Adiponectin: a Manifold Therapeutic Target for Metabolic Syndrome, Diabetes, and Coronary Disease?", CARDIOVASCULAR DIABETOLOGY, vol. 13, no. 103, 2014, pages 1 - 10, XP021193160 * |
MATHER, KJ ET AL.: "Adiponectin, Change in Adiponectin, and Progression to Diabetes in the Diabetes Prevention Program", DIABETES, vol. 57, no. 4, 2008, pages 980 - 986, XP055423526 * |
SNEHALATHA, C ET AL.: "Plasma Adiponectin Is an Independent Predictor of Type 2 Diabetes in Asian Indian s", DIABETES CARE, vol. 26, 2003, pages 3226 - 3229, XP055423536 * |
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