Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes

2021 ◽  
Author(s):  
Łukasz Rzepa ◽  
Michał Peller ◽  
Ceren Eyileten ◽  
Marek Rosiak ◽  
Agnieszka Kondracka ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Waist Circumference ◽  
High Sensitivity ◽  
Model Assessment ◽  
Tnf Α ◽  
Lower Egfr ◽  
Homeostatic Model Assessment ◽  
Factor Α

AbstractThe aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.

scholarly journals Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Khalid M. Mohany ◽  
Osamah Al Rugaie ◽  
Osama Al-Wutayd ◽  
Abdullah Al-Nafeesah
Keyword(s):  
Type 2 Diabetes ◽  
High Sensitivity ◽  
Serum Levels ◽  
Model Assessment ◽  
Obese Children ◽  
Anthropometric Parameters ◽  
Tnf Α ◽  
Homeostatic Model Assessment ◽  
Factor Α

Abstract Aim The present work investigated serum levels of miR-29a, miR-122 and sestrin2 in obese children with/without type-2-diabetes mellitus (T2DM), and their correlations with inflammatory, metabolic and anthropometric parameters. Methods The study included 298 children, divided into: G1 (control, n = 136), G2 (obese without diabetes, n = 90) and G3 (obese with T2DM, n = 72). Metabolic and anthropometric parameters, miR-29a, miR-122 relative expressions, and sestrin2, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured by their specific methods. The data was processed and analyzed by SPSS V.26 using the corresponding tests. After testing the variables’ normality, Kruskal–Wallis one-way-ANOVA, Spearman correlations coefficient were used. Results Significant higher serum miR-29a, miR-122, IL-6, hsCRP and TNF-α and lower sestrin2 levels were found in G2 and G3 than G1 and in G3 than G2 (p= > 0.001 for all). Especially in G3, miR-29a and miR-122 levels correlated positively while sestrin2 levels correlated negatively with waist circumference and BMI percentiles, serum levels of LDL-cholesterol, triacylglycerol, total cholesterol, HbA1c%, glucose, insulin, c-peptide, homeostatic model assessment-insulin resistance (HOMA-IR), IL-6, hsCRP and TNF-α. Conclusion The change in the serum miR-29a, miR-122 and sestrin2 levels in obese children with/without T2DM may suggest a possible role of these biomarkers in the pathogenesis of childhood obesity and their accompanied complications e.g. inflammations and T2DM. Also, further studies are required to test drugs that antagonize the action miR-29a and miR-122 or upregulate sestrin2 in the management of these cases.

scholarly journals Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

2020 ◽  
Vol 8 (1) ◽  
pp. e001425
Author(s):  
Cornelia Then ◽  
Christina Gar ◽  
Barbara Thorand ◽  
Cornelia Huth ◽  
Holger Then ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Vascular Complications ◽  
Model Assessment ◽  
Incident Type ◽  
The Metabolic Syndrome ◽  
Incident Type 2 Diabetes

IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006–2008)/FF4 study (2013–2014).Research design and methodsThe analyses included 1514 participants of the KORA F4 study at baseline and 1132 participants of the KORA FF4 study after a median follow-up time of 6.6 years. All-cause and cardiovascular mortality as well as cardiovascular events were analyzed after a median time of 9.1 and 8.6 years, respectively. The association of PIR with T2D, renal and cardiovascular characteristics and mortality were assessed using logistic regression models. Linear regression analyses were used to assess the association of PIR with components of the metabolic syndrome.ResultsAfter adjustment for sex, age, body mass index (BMI), and physical activity, PIR was associated with prevalent (OR: 2.24; 95% CI 1.81 to 2.77; p<0.001) and incident T2D (OR: 1.66; 95% CI 1.26 to 2.17; p<0.001). PIR was associated with fasting glucose (β per SD: 0.11±0.02; p<0.001) and HbA1c (β: 0.21±0.02; p<0.001). However, PIR was not positively associated with other components of the metabolic syndrome and was even inversely associated with waist circumference (β: −0.22±0.03; p<0.001), BMI (β: −0.11±0.03; p<0.001) and homeostatic model assessment of insulin resistance (β: −0.22±0.02; p<0.001). PIR was not significantly associated with the intima-media thickness (IMT), decline of kidney function, incident albuminuria, myocardial infarction, stroke, cardiovascular or all-cause mortality.ConclusionsIn the KORA F4/FF4 cohort, PIR was positively associated with prevalent and incident T2D, but inversely associated with waist circumference, BMI and insulin resistance, suggesting that PIR might serve as a biomarker for T2D risk independently of the metabolic syndrome, but not for microvascular or macrovascular complications.

scholarly journals The self-nanoemulsifying drug delivery system of Petiveria alliacea extract reduced the homeostatic model assessment-insulin resistance value, interleukin-6, and tumor necrosis factor-α level in diabetic rat models

2021 ◽  
pp. 3229-3234
Author(s):  
Arifa Mustika ◽  
Nurmawati Fatimah ◽  
Gadis Meinar Sari
Keyword(s):  
Insulin Resistance ◽  
Leaf Extract ◽  
Diabetic Rat ◽  
Model Assessment ◽  
Tnf Α ◽  
Significant Difference ◽  
Petiveria Alliacea ◽  
Homeostatic Model Assessment ◽  
Factor Α ◽  
Necrosis Factor

Background and Aim: Metaflammation plays a significant role in the pathogenesis, development, and complication of diabetes mellitus (DM). This inflammation is associated with insulin resistance. Therefore, the inflammatory pathways have been targeted for pharmacological treatment. Petiveria alliacea can decrease blood glucose levels and has anti-inflammatory and antioxidant activities; however, there are still insufficient data regarding its efficacy for the treatment of DM. This study aimed to investigate the effect of the self-nanoemulsifying drug delivery system (SNEDDS) of P. alliacea leaf extract on the homeostatic model assessment (HOMA)-insulin resistance (IR) value and interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) levels in a streptozotocin (STZ)-induced diabetic rat model. Materials and Methods: Thirty-five diabetic rat models were randomly divided into five groups. The first group received the SNEDDS of P. alliacea leaf extract at a dose of 50 mg/kg body weight (BW), the second group received it at a dose of 100 mg/kg BW, the third group received it at a dose of 200 mg/kg BW, the fourth group received 18 mg of metformin, and the fifth group only received the SNEDDS formula. The treatment was administered once a day, orally, for 14 days. On the 15th day after treatment, the rats were sacrificed to obtain blood samples for cardiac examination. The IL-6, TNF-α, and insulin levels in the serum were measured using the enzyme-linked immunosorbent assay method. The HOMA-IR value was calculated using a formula. Results: The mean IL-6 and TNF-α levels were low in the group that received the SNEDDS of P. alliacea leaf extract. There was no significant difference in the insulin level in all treatment and control groups. However, a significant difference in the HOMA-IR value was noted between the group that received the SNEDDS of P. alliacea leaf extract and metformin and the group that did not receive treatment (p<0.05). Conclusion: The SNEDDS of P. alliacea leaf extract reduced the HOMA-IR value and suppressed the TNF-α and IL-6 levels in the STZ-induced diabetic rat model.

scholarly journals Association of Serum Ferritin and Inflammatory Biomarkers with Insulin Resistance in Chinese Type 2 Diabetes Mellitus Patients

2020 ◽  
Vol 1 (7) ◽  
pp. 363-371
Author(s):  
Pratiksha Paudel ◽  
Shitian Zhang ◽  
Bei Guo ◽  
Alisha Pannu ◽  
Gajarishiyan Rasalingam ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Ferritin ◽  
Chinese Population ◽  
Inflammatory Biomarkers ◽  
Model Assessment ◽  
Tnf Α

Objective: Obesity-induced Insulin Resistance (IR) is one of the main causes of Type 2 Diabetes Mellitus (T2DM) and accompanies the progression of T2DM. Serum Ferritin has been shown to be associated with IR. Inflammation is also suggested to be involved in IR and pancreatic β-cell dysfunction. However, there is lack of enough evidence concerning the interrelationship between serum Ferritin, inflammation, and IR in the Chinese population with T2DM. In this study, the relationships between serum Ferritin and inflammatory biomarkers with IR in Chinese population were investigated. Methods: This cross-sectional study was conducted with 207 Chinese participants, aged 40-60 years in Tianjin, China. Serum Ferritin, transferrin, and folate were measured by immuno-assay analyzer. The levels of TNF-α, IL-1β, and IL-6 were detected by ELISA. IR was evaluated by Homeostasis model assessment (HOMA) of IR. Correlations were examined by regression analyses. Results: Serum Ferritin level was higher in non-diabetic obese and diabetic group than the non-diabetic lean group. The levels of TNF-α and CRP were significantly higher in the diabetic obese group than non-diabetic and diabetic lean subjects. Serum Ferritin, TNF-α, and CRP were all correlated with BMI. TNF-α correlated with IR and FPI. TNF-α, IL-6, IL-1β, and CRP were all correlated with FPG and HbA1c. Conclusion: In Chinese population, IR had a significant association with TNF-α but not with serum Ferritin. Serum Ferritin, TNF-α, and CRP were all correlated with BMI. Inflammation and glucose metabolism factors (FPG, HbA1c) showed a strong correlation with each other as well as with adiposity.

scholarly journals The Usefulness of Diagnostic Panels Based on Circulating Adipocytokines/Regulatory Peptides, Renal Function Tests, Insulin Resistance Indicators and Lipid-Carbohydrate Metabolism Parameters in Diagnosis and Prognosis of Type 2 Diabetes Mellitus with Obesity

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1304
Author(s):  
Katarzyna Komosinska-Vassev ◽  
Olga Gala ◽  
Krystyna Olczyk ◽  
Agnieszka Jura-Półtorak ◽  
Paweł Olczyk
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Regulatory Peptides ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Metformin Treatment ◽  
Obese Patients ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model

The quantitative analysis of selected regulatory molecules, i.e., adropin, irisin, and vaspin in the plasma of obese patients with newly diagnosed, untreated type 2 diabetes mellitus, and in the same patients after six months of using metformin, in relation to adropinemia, irisinemia and vaspinemia in obese individuals, was performed. The relationship between plasma concentration of the adipocytokines/regulatory peptides and parameters of renal function (albumin/creatinine ratio—ACR, estimated glomerular filtration rate—eGFR), values of insulin resistance indicators (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR2), Homeostatic Model Assessment of Insulin Sensitivity (HOMA-S), Homeostatic Model Assessment of β-cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI), insulin), and parameters of carbohydrate-lipid metabolism (fasting plasma glucose—FPG, glycated hemoglobin—HbA1C, estimated glucose disposal rate—eGDR, fasting lipid profile, TG/HDL ratio) in obese type 2 diabetic patients was also investigated. Circulating irisin and vaspin were found significantly different in subjects with metabolically healthy obesity and in type 2 diabetic patients. Significant increases in blood levels of both analyzed adipokines/regulatory peptides were observed in diabetic patients after six months of metformin treatment, as compared to pre-treatment levels. The change in plasma vaspin level in response to metformin therapy was parallel with the improving of insulin resistance/sensitivity parameters. An attempt was made to identify a set of biochemical tests that would vary greatly in obese non-diabetic subjects and obese patients with type 2 diabetes, as well as a set of parameters that are changing in patients with type 2 diabetes under the influence of six months metformin therapy, and thus differentiating patients′ metabolic state before and after treatment. For these data analyses, both statistical measures of strength of the relationships of individual parameters, as well as multidimensional methods, including discriminant analysis and multifactorial analysis derived from machine learning methods, were used. Adropin, irisin, and vaspin were found as promising regulatory molecules, which may turn out to be useful indicators in the early detection of T2DM and differentiating the obesity phenotype with normal metabolic profile from T2DM obese patients. Multifactorial discriminant analysis revealed that irisin and vaspin plasma levels contribute clinically relevant information concerning the effectiveness of metformin treatment in T2D patients. Among the sets of variables differentiating with the highest accuracy the metabolic state of patients before and after six-month metformin treatment, were: (1) vaspin, HbA1c, HDL, LDL, TG, insulin, and HOMA-B (ACC = 88 [%]); (2) vaspin, irisin, QUICKI, and eGDR (ACC = 86 [%]); as well as, (3) vaspin, irisin, LDL, HOMA-S, ACR, and eGFR (ACC = 86 [%]).

scholarly journals Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial

2016 ◽  
Vol 174 (2) ◽  
pp. 147-155 ◽  
Author(s):  
Mingyuan Tian ◽  
Zerong Liang ◽  
Rui Liu ◽  
Ke Li ◽  
Xinrong Tan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Oral Glucose ◽  
Model Assessment ◽  
Newly Diagnosed ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Dpp Iv ◽  
Tnf Α ◽  
Pre Treatment

ObjectiveZinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients.Design and methodsA subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations.ResultsCirculating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 orP<0.01), whereas the glucose infusion rate during the stable period of the clamp (Mvalues) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (bothP<0.01) and the change of ZAG (ΔZAG) was positively associated with ΔADI, ΔHOMA-IR, ΔBMI, Δfasting insulin and negatively associated with Δ tumor necrosis factor-α (TNF-α). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-α level (P<0.05).ConclusionA low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.

scholarly journals Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people

2016 ◽  
Vol 115 (8) ◽  
pp. 1379-1386 ◽  
Author(s):  
Kylie A. Abbott ◽  
Martin Veysey ◽  
Mark Lucock ◽  
Suzanne Niblett ◽  
Katrina King ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Model Assessment ◽  
Dietary Interventions ◽  
Overweight Women ◽  
Overweight People ◽  
Homeostatic Model Assessment

AbstractThe association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46·3 % female; 76·7 (sd 5·9) years) and 466 non-diabetic (57·9 % female; 77·8 (sd 7·1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1·0 (reference), 0·82 (95 % CI 0·31, 2·18), 0·56 (95 % CI 0·21, 1·52) and 0·22 (95 % CI 0·06, 0·82) (Ptrend=0·015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences.

scholarly journals Changes in insulin sensitivity during leptin replacement therapy in leptin-deficient patients

2008 ◽  
Vol 295 (6) ◽  
pp. E1401-E1408 ◽  
Author(s):  
Gilberto Paz-Filho ◽  
Karin Esposito ◽  
Barry Hurwitz ◽  
Anil Sharma ◽  
Chuanhui Dong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mixed Model ◽  
Resistance Index ◽  
Oral Glucose ◽  
Model Assessment ◽  
Rapid Weight Gain ◽  
Hypoglycemic Reaction ◽  
Homeostatic Model Assessment

Leptin replacement rescues the phenotype of morbid obesity and hypogonadism in leptin-deficient adults. However, leptin's effects on insulin resistance are not well understood. Our objective was to evaluate the effects of leptin on insulin resistance. Three leptin-deficient adults (male, 32 yr old, BMI 23.5 kg/m2; female, 42 yr old, BMI 25.1 kg/m2; female, 46 yr old, BMI 31.7 kg/m2) with a missense mutation of the leptin gene were evaluated during treatment with recombinant methionyl human leptin (r-metHuLeptin). Insulin resistance was determined by euglycemic hyperinsulinemic clamps and by oral glucose tolerance tests (OGTTs), whereas patients were on r-metHuLeptin and after treatment was interrupted for 2–4 wk in the 4th, 5th, and 6th years of treatment. At baseline, all patients had normal insulin levels, C-peptide, and homeostatic model assessment of insulin resistance index, except for one female diagnosed with type 2 diabetes. The glucose infusion rate was significantly lower with r-metHuLeptin (12.03 ± 3.27 vs. 8.16 ± 2.77 mg·kg−1·min−1, P = 0.0016) but did not differ in the 4th, 5th, and 6th years of treatment when all results were analyzed by a mixed model [ F( 1 , 4 ) = 0.57 and P = 0.5951]. The female patient with type 2 diabetes became euglycemic after treatment with r-metHuLeptin and subsequent weight loss. The OGTT suggested that two patients showed decreased insulin resistance while off treatment. During an off-leptin OGTT, one of the patients developed a moderate hypoglycemic reaction attributed to increased posthepatic insulin delivery and sensitivity. We conclude that, in leptin-deficient adults, the interruption of r-metHuLeptin decreases insulin resistance in the context of rapid weight gain. Our results suggest that hyperleptinemia may contribute to mediate the increased insulin resistance of obesity.

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