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24 INTRODUCTION Kidney transplantation is currently the best alternative treatment for patients with end stage chronic kidney disease Newly transplanted kidneys can function, but patients must take im[.]
1 INTRODUCTION Kidney transplantation is currently the best alternative treatment for patients with end-stage chronic kidney disease Newly transplanted kidneys can function, but patients must take immunosuppressive drugs for life, so they are more susceptible to new diseases such as diabetes New-onset diabetes after transplantation (NODAT) is a complication after organ transplantation in general and kidney transplantation in particular The pathogenesis of NODAT resembles that of type diabetes because it involves insulin resistance and pancreatic beta-cell inhibition Furthermore, kidney transplant recipients have many factors that increase the frequency and severity of NODAT such as several pretransplant factors and the continued use of immunosuppressants Adipose tissue adipokines have a biological role in promoting insulin resistance and pancreatic beta-cell dysfunction Adiponectin and leptin are two highly bioactive adipokines, in which adiponectin positively regulates and leptin negatively regulates insulin secretion and insulin resistance of the pancreas There have been many studies on the role of adiponectin, leptin in patients with type diabetes, however, there are no studies on NODAT patients So I conducted the topic: "Study on plasma adiponectin, leptin levels and relationship with clinical and subclinical characteristics in patients with new-onset diabetes after kidney transplantation." Aims - Investigation of plasma adiponectin and leptin concentrations in patients with new-oset diabetes after kidney transplantation - Analyze the relationship between plasma adiponectin, leptin levels, leptin/adiponectin ratio (LAR) with some clinical and subclinical characteristics in patients with new-onset diabetes after kidney transplantation and the results of follow-up after months Urgency of the study Although the world has confirmed the pathogenesis of NODAT is similar to that of type diabetes, but studies on adiponectin and leptin in NODAT patients have not been much In Vietnam, there are about 20 centers and hospitals nationwide that perform kidney transplants, however, there are not many studies on NODAT Evaluation of the results of blood glucose control in patients with NODAT is also rarely reported Our study results help clinicians control risk factors for NODAT, understand deeply the relationship between adiponectin, leptin and characteristics of NODAT patients as well as treatment outcomes of NODAT patients New main scientific contributions of the thesis - The thesis shows that the level of adiponectin gradually decreased from the normal control group to the non-NODAT and to the NODAT group was significant, p < 0.001 Up to 52.0% of patients decreased plasma adiponectin level In contrast, leptin levels gradually increased from the normal group to the non-NODAT and to the NODAT group, which was significant, p < 0.001 Up to 44.0% of patients increased plasma leptin level and 62.7% of patients increased leptin/adiponectin ratio (LAR) - The concentration of plasma adiponectin, leptin and the leptin/adiponectin ratio are related to BMI and waist circumference The group of overweight and obese patients or increased waist circumference had lower levels of adiponectin, higher leptin levels and the ratio of leptin/adiponectin than the group of patients who were not overweight or obese; not increased waist circumference, p < 0.005 BMI and waist circumference are predictors of decreased adiponectin, p < 0.005; and also predictors of increased leptin, p < 0.005 The concentration of adiponectin, leptin is also related to the results of treatment: The group of patients who did not achieve the goal of blood glucose control had a lower concentration of adiponectin, a higher concentration of leptin than the group of patients who achieved the goal of glucose control, p < 0.05 Thesis structure: Thesis is 119 pages Background: pages, overview: 34 pages, objects and methods: 17 pages, study results: 34 pages, discussion: 28 pages, conclusions and recommendations: pages In the thesis, there are 43 tables, 14 charts, 05 figures References: 149, including Vietnamese and 143 English Chapter 1: OVERVIEW 1.1 NEW-ONSET DIABETES AFTER KIDNEY TRANSPLANT New-onset diabetes after transplantation (NODAT) refers to newly-acquired diabetes following solid organ transplantation in individuals with no previous history of diabetes According to the 2003 International Consensus Guidelines on NODAT, the diagnosis of NODAT is recommended based on the American Diabetes Association (ADA) criteria for diagnosis of type diabetes when one of the following four criteria is present: Fasting blood glucose ≥7.0 mmol/L; Blood glucose at hours after oral glucose tolerance test ≥ 11.1 mmol/L; Any blood glucose ≥ 11.1 mmol/L in symptomatic patients; HbA1C is less recommended during the first year because of anemia 1.1.1 Pathogenesis of NODAT The pathophysiology of NODAT is similar to that of type diabetes: increased insulin resistance and decreased pancreatic beta cell function In NODAT, decreased insulin secretion appears to be more important than glucose intolerance Besides the risk factors for NODAT like the risk factors for type diabetes, there are other factors only seen in the group of posttransplant patients, which is the use of immunosuppressive drugs to maintain organ function such as: Corticosteroids, calcineurin and HCV, CMV infection that cause disturbances in glucose metabolism, decreased secretion and insulin resistance 1.1.2 Some risk factors for NODAT - Non-modifiable risk factors: age, race, gene, and family history are non-modifiable risk factors for the development of NODAT - Some modifiable risk factors: Overweight and obesity, post-transplant viral infection (HCV, CMV), immunosuppressive drugs 1.1.3 Impact of NODAT on kidney transplant function NODAT affects transplant kidney function and survival time of patients According to the results of recent 10-year studies, NODAT is considered as an independent prognostic factor for reduced survival and increased risk factors for all-cause mortality by up to 87% and increased post-transplant failure rates when compared with post-transplant recipients without diabetes The study of Joss N et al surveyed 787 patients after kidney transplantation with and 10-year survival rates of 86.1% and 67.1%, respectively, in patients who developed NODAT, significantly lower compared with 90.9% and 81.9% in those who did not develop NODAT (p < 0.01) Based on this evidence, it is paramount to detect diabetes in these subjects for pre-transplant intervention The 2-hour oral glucose tolerance test (OGTT) can help detect diabetes and pre-diabetes early Furthermore, the highest rates of developing NODAT usually occur within the first year after transplantation Therefore, screening for NODAT early after transplantation is recommended 1.2 ADIPONECTIN AND LEPTIN IN DODAT PATIENTS Among the adipokines of adipose tissue, adiponectin and leptin are two adipokines with high biological activity, in which adiponectin regulates positively and leptin negatively regulates insulin secretion and insulin resistance The role of these two adipokines has also been confirmed in the pathogenesis of NODAT after renal transplantation 1.2.1 Adiponectin - Secreted mainly from adipose tissue, little from liver, muscle - Adiponectin is a protein with a MW of 28 kDa, including 244 aa Metabolized by the liver, excreted by the kidneys - Role: Increase insulin sensitivity, metabolism of carbohydrates and blood lipids, anti-inflammatory, anti-atherosclerotic, anti-tumor 1.2.2 Leptin - Secreted mainly from adipose tissue, but also from the intestine - Leptin is a hormone with a MW of 16 kDa, including 167 amino acids Metabolized by the liver and eliminated by the kidneys - Role: Regulating food intake, energy homeostasis (both excess and deficiency) causing weight loss, neuroendocrine, insulin resistance, lipid metabolism, plays a role in immunity, reproduction, cytokines… 1.2.3 Leptin/adiponectin ratio (LAR) Leptin and adiponectin interact in regulating the risk of type diabetes, but adiponectin may have a stronger association with the risk of type diabetes (T2D) There is an inverse relationship between leptin and adiponectin in patients with T2D and in obese patients Although leptin or adiponectin was separately associated with the risk of metabolic syndrome and type diabetes, the association of type diabetes risk with LAR was stronger than with leptin or adiponectin alone LAR is a useful predictor of insulin resistance in clinical practice and a good indicator to evaluate the effectiveness of diabetes therapy In patients with obesity and type diabetes, there is a concentration reversal: leptin levels increase, while adiponectin levels decrease 1.3 RELATED STUDIES - In the world: Research on adiponectin concentration: increased in patients with CKD, decreased after kidney transplantation Leptin levels: increased in patients with CKD and associated with cardiovascular events, levels will decrease after transplantation - In the country: Some studies show that adiponectin concentration decreases in the obese group compared with the control group, whereas leptin increases in the obese group; prediabetes compared with normal controls There are no studies in patients with NODAT Chapter 2: SUBJECTS AND METHODS 2.1 SUBJECTS - Study subjects: 252 people were divided into groups: NODAT group (75 people), control group (102 people) and normal control group (75 people) Research place: Department of Nephrology and Dialysis, Military Hospital 103 Time: 12/2019 - 12/2021 2.1.1 Criteria for study group (NODAT group) - Before transplantation: no diabetes, no impaired glucose tolerance - Patients diagnosed with NODAT for the first time or have been diagnosed Duration kidney transplant ≥ months Age ≥ 18 years old - Receive treatment against transplant rejection and other disorders as recommended by the Vietnam organ transplantation Association - Patients cooperate and participate in research 2.1.2 Criteria for control group (Non-NODAT Group) - Before transplantation: no diabetes, no impaired glucose tolerance - After kidney transplant without NODAT, no impaired glucose tolerance Duration kidney transplant ≥ months Age ≥ 18 years old - Receive treatment against transplant rejection and other disorders as recommended by the Vietnam organ transplantation Association - Patients cooperate and participate in research 2.1.3 Criteria for normal control group - Adults who go for a health check-up are found to be normal - Have a fasting blood glucose level < 5.6 mmol/L - No history of kidney-urinary disease - Age and gender similarity with the study group - Agree to participate in the study 2.1.4 Exclusion criteria for NODAT and control groups - Patients with diabetes or impaired glucose tolerance before transplantation - At the time of the study, they were suffering from acute diseases such as infection, myocardial infarction, cerebral stroke, acute pancreatitis - Patients with suspected surgical disease - Pregnant or lactating women - The patient did not meet the study criteria 2.2 STUDY CONTENTS AND METHODS 2.2.1 Study design and sample size - Carrying out cross-sectional descriptive study, longitudinal follow-up - Selecting convenient sample for the study, we have results: 75 patients in NODAT group, 102 patients in control group and 75 people in normal control group The total number of study subjects is 252 2.2.2 Study Indicators Criteria for common characteristics: - Asking age (year), gender, pre-transplant treatment for renal failure, pre-transplant immune factors Clinical and subclinical criteria - The patient has clinical symptoms or not Time after transplant Several pre-transplant risk factors Time to detect NODAT: first or diagnosed Post-transplant therapy - Measure height, weight, calculate BMI Measuring waist circumference determines abdominal obesity Blood pressure status - Complete blood count test: determine the degree of anemia - Blood biochemical tests: concentration of albumin, protein, CRP, creatinine, blood lipids, urine Calculate GFR according to MDRD formula 2.2.3 Quantification of plasma adiponectin and leptin levels - Quantitative place: Department of Pathophysiology - Military Medical University - Blood samples: IV fasting, anticoagulation with EDTA, centrifugation to collect plasma Method: ELISA - Units: adiponectin: μg/mL and leptin: ng/mL - Evaluation of results: Evaluation of increase/decrease in adiponectin, leptin concentrations based on biological indices of the normal group: Because the above indices are not distributed according to normal laws, they should be based on the 2.5 -97.5 percentile of controls determined to increase or decrease concentration - Reference range of the 2.5-97.5 percentile of the normal control group: Adiponectin: 25,89 - 88,17; leptin: 1,06 - 4,50; LAR: 0,01 - 0,12 2.2.4 Monitoring treatment and evaluating results after months of follow-up of NODAT - Patients receive personalized treatment Medications to lower blood glucose: include insulin and oral medications - All patients were re-tested fasting blood glucose monthly Adjust dose according to blood glucose concentration - After months, only 52 remaining patients - Evaluation criteria after months: Anemia, Hb concentration Fasting blood glucose levels, blood urea and creatinine, GFR calculation Quantification of plasma CRP, proteinuria - Assess fasting blood glucose control at months - As recommended: + Targeted control: blood glucose < 7.0 mmol/L + Failure to achieve the target: blood glucose ≥ 7.0 mmol/L 2.3 Data Processing Enter data into ecxel, using SPSS 20.0 software - Calculate mean and median Compare percentages and averages Determine the correlation, determine the difference ratio - Multivariate logistic analysis to identify independent factors - Draw ROC curve to determine risk predictor Chapter 3: RESULTS 3.1 GENERAL CHARACTERISTICS OF RESEARCH SUBJECTS Table 3.1 Comparison of age among study subjects Normal control Non-NODAT NODAT group group group (n=75) (n=102) (n=75) Age p chac number number number of rate % of rate % of rate % patients patients patients < 40 age 25 33,3 43 42,2 28 37,3 40 - < 50 25 33,3 36 35,3 19 25,3 age > 0,05a 50 - < 60 24 32 15 14,7 22 29,3 age ≥ 60 age 1,3 7,8 Mean (ages), 44,11 ± 8,19 43,29 ± 9,0 44,88 ± 11,34 > 0,05b ( X ± SD) a Fisher's Exact test, b one-way ANOVA test - There is no difference in mean age between NODAT, non-NODAT and normal group, p > 0.05 Table 3.2 Comparison of gender among study subjects Normal Non-NODAT NODAT Gender control group group group Characteristic (n=75) (n=102) (n=75) p s patients rate Patients rate Patients rate % % % 31, Female 24 32 32 24 32 > 68, Male 51 68 70 51 68 0,05c Total 75 100 102 100 75 100 c Chi-square test; - There is no difference in gender between NODAT, non-NODAT and normal group, p > 0.05 Table 3.5 Pre-transplant risk factors associated with NODAT Non-NODAT NODAT group group (n=102) (n=75) P patients rate % patients rate % Diabetic family 17 16,8 25 33,3 < 0,05 c history Age > 60 7,8 > 0,05 c Infected HCV 26 25,5 23 30,7 > 0,05 c c Chi-square test - The NODAT group had a significantly higher rate of family-related diabetes than the non-NODAT group, p < 0.05 Table 3.8 Comparison of BMI between the groups BMI Non-NODAT NODAT group P (kg/m2) group (n=102) (n=75) patients rate % patients rate % < 18,5 17 16,7 14 18,7 18,5 to 22,9 67 65,7 27 36 < 0,001 c ≥ 23 18 17,6 34 45,3 Mean, 20,99 ± 2,39 22,32 ± 3,05 < 0,005 d (kg/m2), ( X ± 10 SD) c Chi-square test, d student T test - There was a significant difference in BMI between the NODAT and non-NODAT groups, p < 0.01 Table 3.9 Comparison of waist circumference between groups Non-NODAT NODAT group P group (n=102) (n=75) patients rate % patients rate % Fat belly: - Male ≥ 90 cm 11 10,8 25 33,3 < 0,001 c - Female ≥ 80 cm Mean, (cm), 73 (68 – 82) 76 (68 – 91) < 0,05 e ( X ± SD) c Chi-square test, e Mann-Whitney U test - The percentage of patients with increased waist circumference in the NODAT group was significantly higher than in the non-NODAT group, p < 0.001 3.2 CHARACTERISTICS OF ADIPONECTIN, LEPTIN LEVELS AND LEPTIN/ADIPONECTIN RATIO IN NODAT PATIENTS Table 3.15 Comparison of adiponectin, leptin concentrations between groups Normal NonNODAT P control NODAT group group group (n=75) (n=75) (n=102) Adiponectin (µg/mL) Median (Inter.) 45,65 (34,19 – 60,75) 37,78 (28,98 – 42,8) 24,78 (9,56 – 51,91) < 0,001 f Leptin (ng/mL) Median (Inter.) 2,45 (1,92 – 3,86) 4,01 (3,08 – 4,65) 4,22 (3,01 – 5,39) < 0,001 f LAR (ng/µg) Median (Inter.) 0,06 (0,04 – 0,1 (0,08 – 0,14) 0,17 (0,09 – < 0,001 f 12 Decrease adiponectin and increase leptin, n 3,9 17 22,7 (%) c Chi-square test - The NODAT group had a lower rate of patients with normal plasma adiponectin and leptin levels than the group of post-transplant patients without NODAT, p < 0.001 -In contrast, the NODAT group had a significantly higher percentage of patients with abnormality in both indexes than the group without NODAT, p < 0.001 3.3 RELATIONS BETWEEN ADIPONECTIN, LEPTIN, LEPTIN/ADIPONECTIN RATIO WITH SOME CLINICAL AND PARACLINICAL FEATURES IN PATIENTS WITH NODAT 3.3.1 Relationship between adiponectin concentration, leptin, leptin/adiponectin ratio with some clinical and subclinical characteristics Table 3.21 Comparison of adiponectin, leptin concentrations in detected and newly detected NODAT groups Indicators Treated None- Treated NODAT p NODAT (n=52) (n=23) Adiponectin Median 21,5 29,83 > 0,05 (Inter.) (9,75 – 55,1) (9,55 – 46,37) e (µg/mL) Leptin (ng/mL) LAR (ng/µg) Median 3,89 4,36 > 0,05 (Inter.) (2,98 – 5,17) (3,03 – 5,42) e Median 0,17 0,17 > 0,05 (Inter.) (0,09 – 0,27) (0,09 – 0,32) e e Mann-Whitney U test, c Chi-square test - There was no significant difference in the concentration of plasma adiponectin, leptin and leptin/adiponectin ratio in the group of newly diagnosed and diagnosed NODAT patients, p > 0.05 Table 3.23 Correlation of adiponectin, leptin levels with overweight and obesity BMI ≥ 23 BMI < 23 OR, p (n=34) (n=41) Adiponectin Median 9,91 30,99 < 0,05 e 13 (µg/mL) Leptin (ng/mL) LAR (ng/µg) (Inter.) (9,35 – 48,91) (17,47 – 54,43) 3,76 (2,88 – 5,16) 0,14 (0,08 – 0,23) Median 5,17 < 0,05 e (Inter.) (3,79 – 5,44) Median 0,26 < 0,005 (Inter.) (0,1 – 0,54) e Mann-Whitney U test, c Chi-square test - In the overweight and obese NODAT group, the concentration of adiponectin was lower, the level of leptin and the ratio of leptin/adiponectin higher than the group of NODAT patients who were not overweight, obese, p < 0.05 Table 3.24 Correlation between adiponectin, leptin levels and BMI BMI (kg/m2) Equation r p Adiponectin < Adiponectin = 71,426 – (µg/mL) 0,295 0,05 1,896*BMI Leptin 0,302 < Leptin = 0,132*BMI + 1,336 (ng/mL) 0,01 LAR (ng/µg) 0,488 < LAR = 0,027*BMI – 0,363 0,001 - There was a significant negative correlation between adiponectin, a significant positive correlation between leptin concentration, leptin/adiponetin ratio with BMI in NODAT patients, p < 0.05 Table 3.25 Concentrations of adiponectin, leptin with abdominal obesity in the NODAT group Fat belly Not fat belly OR, p (n=25) (n=50) Adiponectin Media 30,95 9,87 (µg/mL) n (15,62 – < 0,01e (9,34 – 26,33) (Inter.) 54,78) Leptin Media 5,18 3,84 (ng/mL) n < 0,05 e (4,0 – 5,63) (2,89 – 5,16) (Inter.) LAR (ng/µg) Media 0,38 0,14 < 0,001 e n (0,17 – 0,55) (0,08 – 0,24) (Inter.) e Mann-Whitney U test, c Chi-square test - In the NODAT group with abdominal obesity, the concentration of adiponectin was lower, the levle of leptin and the ratio of 14 leptin/adiponectin were significantly higher than that of the NODAT group without abdominal obesity, p < 0.05 15 Table 3.29 Comparison of adiponectin, leptin levels in the group with and without reduction in glomerular filtration rate GFR < 60 GFR ≥ 60 P ml/min ml/min (n=60) (n=15) Adiponectin Median 35,67 20,46 (µg/mL) (Inter.) (24,78 – < 0,05 e (9,49 – 41,5) 59,27) Leptin Median 5,42 3,93 < 0,005 e (ng/mL) (Inter.) (3,89 – 6,13) (2,91 – 5,18) LAR Median 0,12 0,18 > 0,05 e (ng/µg) (Inter.) (0,08 – 0,23) (0,09 – 0,32) e Mann-Whitney U test, c Chi-square test - The group of patients with decreased GFR had higher levels of adiponectin, leptin than the group without GFR reduction, p < 0.05 Figure 3.10 ROC curve predicts decrease in Adiponectin Comment: BMI and waist circumference are predictors of decreased adiponectin concentration in NODAT patients, p < 0.005 Figure 3.10 ROC curve predicts decrease in Adiponectin Comment: BMI and waist circumference are predictors of decreased adiponectin concentration in NODAT patients, p < 0.005 16 Figure 3.11 ROC curve predicts increase in Leptin Comments: BMI and waist circumference are predictors of increased leptin levels in NODAT patients, p < 0.005 3.3.2 Results of blood glucose control and some indicators after months of follow-up Table 3.34 Characteristics of patient change after months of followup Characteristics Number of Rate % pantients NODAT patients at month 75 100,0 Remaining patients at month 52 69,3 - After months of follow-up, the number of remaining patients was 52, accounting for 69.3% 17 Table 3.35 Transformation of some indexes before and after months (n=52) Indicators Month Month p (n=52) (n=52) Blood Glucose 6,16 ± 1,73 6,79 ± 2,83 > 0,05 i (mmol/l), ( X ± SD) Anemia, n (%) 13 (25) (13,5) > 0,05 k Ure(mmol/L),( X ± SD) 5,95 ± 1,73 6,6 ± 1,89 < 0,005 i Creatinine (µmol/L),( 98,53 ± 99,59 ± > 0,05 i X ± SD) 22,5 22,13 CRP (mg/L), Median 1,29 (0,73 1,38 (0,71 – > 0,05 j (Inter.) – 2,56) 2,8) Proteinuria (+), n (1,9) (11,5) > 0,05 k i Paired-sample T test, j Wilcoxon test, k Mc Nemar test - There was only a significant difference in blood urea level at T0 and after months of treatment, p < 0.005 Figure 3.13 Percentage of patients with blood glucose control reaching the recommended target (n=52) - Most of the NODAT patients had their blood glucose controlled at the target level, only 25.0% of the patients with the blood glucose control did not reach the target 18 Table 3.38 Comparison of adiponectin, leptin levels at time month between the group achieving and not achieving the goal of blood glucose control Indicators Not Achieve Achieve goals p goals (n=13) (n=39) Adiponectin (µg/mL), 17,07 31,67 < 0,05 e Median (Inter.) (9,2 – 27,28) (11,3 – 54,18) Leptin (ng/mL), Median 4,87 3,54 < 0,05 e (Inter.) (3,39 – 5,4) (2,74 – 4,33) LAR (ng/µg), Median 0,27 0,11 < 0,005 e (Inter.) (0,16 – 0,49) (0,09 – 0,22) e Mann-Whitney U test - The control group that did not reach the goal had a lower concentration of adiponectin, a higher level of leptin, and a higher ratio of leptin/adiponectin than the group of patients with blood glucose control reaching the goal, p < 0.05 Chapter 4: DISCUSSION 4.1 GENERAL CHARACTERISTICS OF STUDY OBJECTS The results of our study showed that the mean age of the study group was 44.88 ± 11.34 years old, of which only 8.0% of patients were over 60 years old The study of Nishimura K et al in 2009 had an average age of 48.5 years, and Adachi H et al in 2020 had an average age of 41.0 years Thus, the studies on kidney transplant subjects showed similar results The study by Rysz et al showed that age > 45 years had a 2.2 times higher risk of NODAT compared with age 18-44 4.2 CHARACTERISTICS OF PLASMA ADIPONECTIN, LEPTIN The results of our study show that there is an inverse relationship between plasma adiponectin and leptin concentrations in the NODAT group and the non-NODAT group, p < 0.001 4.2.1 Adiponectin concentration characteristics When comparing adiponectin concentrations with some authors on NODAT subjects such as Bayés B et al in 2007 and Nishimura K et al in 2012, we found a similarity 19 Table 4.1 Comparison of adiponectin concentrations with some other authors Mean/ Median Authors Objects (μg/mL) -45 NODAT patients: mean age: 54 years old, male: 57.8%, average time of kidney transplant was 69.6 Bayés B et months - 104 patients without NODAT: al 2007 mean age 53, male: 66.2%, average time of kidney transplant was 68.8 months -11 NODAT patients: mean age 53.1 ± 10.3 years old, male: 54.5%, average kidney transplant time 62.3 ± 48.5 months Nishimura - 79 patients after transplantation K et al 2012 without NODAT: The mean age was 45.9 ± 11.3 years old, male: 59.5%, the average time of kidney transplant was 64.8 ± 33.2 years -75 NODAT patients: mean age 44.88 ± 11.34 years old, male: 68.0%, average kidney transplant time 14.17 months - 102 patients without NODAT: The Ours 2021 mean age was 43.29 ± 9.0 years old, male: 68.6%, the average time of kidney transplant was 16.57 months - 75 normal people of the same age and sex 11,25 ± 5,04 16,32 ± 6,52 11,9 16,4 24,78 (9,5651,91) 37,78 (28,98 – 42,8) 45,65 (34,19 – 60,75) All studies confirmed that plasma adiponectin concentrations in NODAT patients were lower than those of non-NODAT and normal group This is explained by the concentration of adiponectin related to blood glucose metabolism 20