Vascular responses to α-adrenergic stimulation and depolarization are enhanced in insulin-resistant and diabetic Psammomys obesus

2003 ◽  
Vol 81 (7) ◽  
pp. 704-710 ◽  
Author(s):  
M Zoltowska ◽  
J St-Louis ◽  
E Ziv ◽  
B Sicotte ◽  
E E Delvin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vascular Reactivity ◽  
Vascular Complications ◽  
Psammomys Obesus ◽  
Adrenergic Stimulation ◽  
Endothelial Lining ◽  
Insulin Resistant ◽  
Group A ◽  
Group B ◽  
Endothelium Dependent Relaxation

Since vascular complications often accompany diabetes, we examined the influence of the endothelial lining on vascular reactivity in Psammomys obesus, a desert gerbil that acquires insulin resistance and diabetes when exposed to a laboratory diet. Vasoconstriction to phenylephrine and depolarizing KCl, as well as carbachol endothelium-dependent relaxation, were assessed in rings of thoracic aortae obtained from three groups: (i) group A, normoglycemic–normoinsulinemic; (ii) group B, normoglycemic–hyperinsulinemic, and (iii) group C, hyperglycemic–hyperinsulinemic animals. As expected, marked hypertriglyceridemia and hypercholesterolemia characterized groups B and C, which developed enhanced contractile responsiveness to phenylephrine and KCl compared with controls (group A). Furthermore, both experimental groups displayed a significant decrease in endothelium-dependent relaxation to carbachol. Altered lipid profiles are considered to play some role in the observed modification of aortic reactivity. Overall, our data indicate that vascular contractile responsiveness is enhanced early in the development of insulin resistance and diabetes in the female P. obesus.Key words: insulin resistance, diabetes, vascular reactivity, LDL-cholesterol, hypertriglyceridemia.

P713Short term treatment of a low dose erythropoietin improves vascular function in a rat model of insulin resistance

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Toba ◽  
A Yamaoka ◽  
S Sakurai ◽  
Y Tanaka ◽  
A Miyamoto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Vascular Function ◽  
Insulin Signalling ◽  
Term Treatment ◽  
Protective Effects ◽  
Insulin Resistant ◽  
Induce Insulin Resistance ◽  
Group A ◽  
Group B

Abstract Background/Introduction Erythropoietin (EPO) exerts haematopoiesis-independent cardiovascular and renal protective effects by binding to EPO receptors expressed in hearts, arteries, and kidneys. We have reported that EPO inhibits vascular and renal injury in rat models of hypertension and type 1 diabetes. Recent studies report that EPO improves glucose tolerance in insulin resistant animals. Purpose This study investigated whether EPO would inhibit vascular and renal dysfunction in the setting of insulin resistance. Methods Rats were treated with sucrose (12% in drinking water) for 10 weeks to induce insulin resistance. EPO (3 times/week, s.c) was administered at the dose of 150U/kg for 10 weeks from the beginning (group A) or at the dose of 75U/kg for the last 4 weeks (group B) of sucrose treatment. Blood pressure was measured every second week by the tail-cuff method. HOMA-IR, haematocrit, and urinary protein excretion were measured. Using isolated aortas, acetylcholine-induced vasorelaxation under phenylephrine-induced pre-contraction was examined. Aortic sections were stained with haematoxylin-eosin. Results Both groups A and B showed higher haematocrit levels compared with the control and sucrose alone-treated groups. Sucrose treatment increased HOMA-IR (7.7±2.0 vs. 24±4.5, p<0.05), which was attenuated in groups A (3.6±0.9) and B (9.7±4.0). EPO treatment (150U/kg) had no effects on blood pressure for the first 4 weeks but caused time-dependent increases in blood pressure from the 6th week. Increased proteinuria and impaired aortic vasorelaxation in sucrose-treated rats were exacerbated by EPO (150U/kg) maybe because of hypertension (Control 122±2mmHg, Sucrose 125±2mmHg, group A 148±5mmHg), one of the major side effects of EPO. According to these results, we treated a half dose of EPO only for the last 4 weeks (group B). A lower dose of EPO treatment for a shorter period did not increase proteinuria (Control 15±2mg/day, Sucrose 25±3mg/day, group B 24±3mg/day) despite a mild increase in blood pressure (132±2mmHg). Impaired endothelium-dependent vasodilation and aortic thickening in the aorta of sucrose alone-treated rats were attenuated by lower and shorter EPO treatment (group B). Conclusions EPO inhibited insulin resistance and vascular injury in sucrose-induced insulin resistant rats. Further investigation into the mechanisms of tissue protective effects of EPO, especially focusing on the effects on insulin signalling in not only hepatic and muscle cell but also vascular and renal cells, will be needed.

scholarly journals To study levels of serum fibrinogen in type 2 diabetes mellitus and its association with diabetic microvascular complications

2017 ◽  
Vol 4 (1) ◽  
pp. 10
Author(s):  
Gurinder Mohan ◽  
Ranjeet Kaur ◽  
Aakash Aggarwal ◽  
Parminder Singh
Keyword(s):  
Diabetes Mellitus ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
High Serum ◽  
Diabetic Patients ◽  
Coagulation Disorder ◽  
Urine Albumin ◽  
Group A ◽  
Diabetic Microvascular Complications ◽  
Group B

Background: Diabetes mellitus is a hypercoagulable state associated with atherosclerosis leading to development of vascular complications, including microvascular complications.Methods: In our study a total of 60 diabetic patients with duration of diabetes more than 5 years, attending the OPD/ indoor of SGRDIMSR, Amritsar, Punjaqqb, India were included. They were divided in two groups, group A of 30 patients including diabetics with any of the three microvascular complications (diabetic nephropathy, diabetic retinopathy and diabetic neuropathy) and group B of 30 patients including diabetics without any microvascular complication. Group C comprised of 30 age and sex matched non-diabetic subjects who served as controls. Subjects with liver cirrhosis, malignancy or coagulation disorder were excluded. After taking the consent, detailed history taking and detailed physical examination and relevant investigations were done. The serum fibrinogen (hemostasis marker), HBA1C and UACR (urine albumin creatinine ratio) along with routine investigations were measured.Results: It was observed that serum fibrinogen levels were significantly higher in diabetic patients (266.16±54.73 mg/dl) as compared to non-diabetic controls (174.66±18.32 mg/dl); p <0.001.Further, serum fibrinogen levels were found to be significantly higher in diabetic patients with microvascular complications (293.43±51.09 mg/dl) as compared to those without microvascular complications (238.90±44.12); p<0.001.Conclusions: Significantly high serum fibrinogen level was found in diabetic patients as compared to controls and was in positive correlation with development of microvascular complications.

P–662 Study on D-vitamin, AMH and insulin interrelation in Polycystic Ovary Syndrome (PCOS) patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Coc. Lizarraga ◽  
S Lindenberg ◽  
G Juu. Almind ◽  
F Lindenberg
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Serum Vitamin ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Group A ◽  
D Values ◽  
Group B

Abstract Study question Is vitamin D deficiency more prevalent in PCOS patients? Is there a link between vitamin D levels and metabolic status in PCOS subjects? Summary answer An inverse relationship between vitamin D levels and metabolic status was demonstrated and it is thought to be responsible of its pathogenesis. What is known already PCOS is a multifactorial condition, characterised by failure in oogenesis and anovulation. Obesity is a common condition linked to its clinical features and studies have reported inverse associations between BMI and severity of the condition. Furthermore, 67–85% of PCOS patients have vitamin D deficiency. Low levels of vitamin D have been found to be closely related to insulin resistance, obesity, or hyperandrogenism and there is a significant association between serum vitamin D levels and reproductive function. Other factors such as AMH have also been described as possibly involved in the pathophysiology. Study design, size, duration We performed a retrospective, analytical and observational study in the Copenhagen Fertility Center. Patients referred with cycle abnormalities, hirsutism, and infertility were evaluated. A total of 778 women were enrolled consecutively from January 2019 to October 2020. Subjects who had major medical disorders were excluded. We selected those in which vitamin D was measured in the baseline analysis selecting a total of 396 patients. The further analysis has been carried out from 100 randomly selected patients. Participants/materials, setting, methods Blood samples were drawn after overnight fasting. They were all assayed in the same laboratory. Biochemical parameters were analyzed using descriptive statistics. Same parameters were studied after dividing into vitamin D deficiency group or optimal levels using a multiple t-test. Correlation between variables was determined. Graphpad Prism program version 8 was used to perform the calculations. The level of statistical significance was set at P-value &lt; 0.05. Main results and the role of chance A total of 100 subjects fulfilling the inclusion criteria were selected randomly from 396 PCOS women. Serum vitamin D concentrations were highly variable ranging from 16 nmol/L to 175 nmol/L. The prevalence of vitamin D deficiency was 24% and 41% of the subjects were classified as vitamin D insufficient. Only 35% of our patients had optimal vitamin D values. We compared data between the group with optimal values of vitamin D (Group A) versus the group with insufficient/deficient vitamin D values (Group B). We found statistical difference between groups in PTH values, being notably higher in group B compared with group A. Despite no statistically significant difference was obtained, it is important to highlight that the mean of SHBG was lower in group B and the mean of androstenedione, AMH, FAI and HOMA-IR were much higher in this group as well. Following the HOMA-IR criteria, 55% of patients had insulin resistance. Specifically, 26% had moderate insulin resistance and 29% severe insulin resistance. Levels of vitamin D were negatively correlated with FAI, AMH and HOMA-IR and positively correlated with HDL-Cholesterol and SHBG. Statistically significant differences were evidenced in the correlation between vitamin D and FAI and SHBG. Limitations, reasons for caution This is a retrospective observational study on a consecutive admitted patient group with a lack of a control group. Another limitation is the small sample size. It is difficult to generalize with other degrees of severity. We didn’t assess seasonal variability or if they were taking any vitamin D supplementation. Wider implications of the findings: Properly randomized clinical trials are mandatory to achieve more conclusive results about the role of vitamin D. Available evidence is promising but not sufficient to draw final conclusions. The aim is to better understand the pathophysiology of the condition and the factors involved and to find new target treatments. Trial registration number 1

Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat

2007 ◽  
Vol 293 (4) ◽  
pp. H2537-H2542 ◽  
Author(s):  
David W. Stepp ◽  
Erika I. Boesen ◽  
Jennifer C. Sullivan ◽  
James D. Mintz ◽  
Clark D. Hair ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Zucker Rats ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Insulin Resistant

Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.

Generalized impairment of vasodilator reactivity during hyperinsulinemia in patients with obesity-related metabolic syndrome

2010 ◽  
Vol 299 (6) ◽  
pp. E947-E952 ◽  
Author(s):  
Francesca Schinzari ◽  
Manfredi Tesauro ◽  
Valentina Rovella ◽  
Angelica Galli ◽  
Nadia Mores ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Vitamin C ◽  
Vascular Reactivity ◽  
Vascular Complications ◽  
Glucose Disposal ◽  
Vascular Abnormalities ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
Before And After

Defective insulin-dependent vasodilation might contribute importantly to metabolic and vascular abnormalities of the metabolic syndrome (MetS). However, despite extensive investigation, the precise mechanisms involved in insulin's vasoactive effects have not been fully elucidated. Therefore, this study sought to better characterize insulin's physiological actions on vascular reactivity and their potential derangement in the MetS. Forearm blood flow responses to graded doses of acetylcholine, sodium nitroprusside, and verapamil were assessed by strain-gauge plethysmography in patients with obesity-related MetS ( n = 20) and in matched controls ( n = 18) before and after intra-arterial infusion of insulin (0.2 mU·kg−1·min−1). Possible involvement of increased oxidative stress in the impaired insulin-stimulated vasodilator responsiveness of patients with MetS ( n = 12) was also investigated using vitamin C (25 mg/min). In control subjects, significant potentiation of the vasodilator responses to acetylcholine, nitroprusside, and verapamil was observed after insulin infusion (all P < 0.05). However, no significant change in vasodilator reactivity to either of these drugs was observed following hyperinsulinemia in patients with MetS (all P > 0.05). Interestingly, administration of vitamin C to patients with MetS during hyperinsulinemia significantly enhanced the vasodilator responsiveness to acetylcholine, nitroprusside, and verapamil (all P < 0.05 vs. hyperinsulinemia alone). In conclusion, insulin exerts a generalized facilitatory action on vasodilator reactivity, and this effect is impaired in patients with MetS likely because of increased oxidative stress. Given the importance of vasodilator reactivity in affecting glucose disposal and vascular homeostasis, this defect may then contribute to the development of metabolic and vascular complications in insulin-resistant states.

scholarly journals NORMAL VASCULAR REACTIVITY IS RESTORED BY APIGENIN IN DIABETIC RATS

2018 ◽  
Vol 10 (1) ◽  
pp. 27
Author(s):  
Hany M. El-bassossy ◽  
Nora Desoky ◽  
Abdulrahman M Alahdal ◽  
Ahmed Fahmy
Keyword(s):  
Insulin Resistance ◽  
Potassium Chloride ◽  
Sodium Nitroprusside ◽  
Vascular Reactivity ◽  
Antioxidant Properties ◽  
Diabetic Rats ◽  
Insulin Deficiency ◽  
Insulin Resistant ◽  
The Impact

Objective: Diabetes is a disease whose complications have serious implications for the health of sufferers; one of the most serious such complications is the deterioration of vascular reactivity. Apigenin is a natural flavonoid with PKC inhibiting and antioxidant properties. In this study, the impact of apigenin on vascular reactivity deterioration was investigated.Methods: Insulin resistance (IR) and insulin deficiency (ID) were induced by fructose and streptozotocin respectively. The isolated aortae vasoconstriction response to phenylephrine (PE) and potassium chloride (KCl) in addition to the vasodilation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were tested.Results: IR and ID were associated with significantly exaggerated vasoconstriction to KCl and PE while significantly impaired vasodilation to ACh. Response to SNP was not significantly affected by both IR and ID. In vitro incubation with apigenin (7 7µM) for 20 min restored normal responses to PE, KCl and ACh in aortae isolated from insulin-resistant or insulin-deficient rats. Incubation for one hour with the PKC stimulant, phorbol 12-myristate 13-acetate (PMA, 800 nM) resulted in aortic impairment similar to that seen in aortae isolated from IR and ID animals. Incubation with both apigenin prevented PMA-induced exaggerated vasoconstriction response to both PE and KCl.Conclusion: Apigenin alleviates vascular exaggerated vasoconstriction and impaired dilation associated with diabetes or PKC activated.

scholarly journals Low molecular weight heparins use in pregnancy: a practice survey from Greece and a review of the literature

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
E. Papadakis ◽  
A. Pouliakis ◽  
Α. Aktypi ◽  
A. Christoforidou ◽  
P. Kotsi ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Scientific Evidence ◽  
Vascular Complications ◽  
Bleeding Events ◽  
History Of ◽  
Group A ◽  
Major Bleeding Events ◽  
Diagnostic Work ◽  
Group B ◽  
In Pregnancy

Abstract Background Use of LMWH in pregnancy is not only limited to VTE management, but it extends, to the management of vascular gestational complications and the optimization of IVF pregnancies despite the lack of concrete scientific evidence. In this context, we conducted the present study aiming to gain insights regarding the use of LMWH during pregnancy and puerperium. We recorded indication for use, diagnostic work-up as well as the safety and efficacy of the treatment, trying to elucidate the clinical practice in our country. Methods We analyzed data regarding 818 pregnant women received LMWH during 2010–2015.Our cohort had a median age of 33.9 years and a BMI of 23.6.There were 4 groups: those with a history of VTE [Group-A: 76], those with pregnancy complications [Group-B: 445], those undergoing IVF [Group-C: 132] and those carrying prothrombotic tendency (thrombophilia, family history of VTE, other) [Group-D: 165]. Mean duration of LMWH administration was 8.6 ± 1.5 months. Out of the total number, 440 received LMWH in fixed prophylactic dose, 272 in higher prophylactic-weight adjusted dose and 106 in therapeutic dose. Moreover, 152 women received in addition low-dose acetylsalicylic acid (ASA). 93.8% of pregnancies were single and 6.2% were multiple ones. Live births occurred in 98.7% of pregnancies. Results Anticoagulation was efficacious and well tolerated. Seventeen VTE events were recorded; 7 of them antepartum and 10 postpartum. No major bleeding events were observed while 13 clinical relevant non-major bleeding events were recorded. Regarding gestational vascular complications, 28 IUGR events were recorded, as well as 48 cases of preterm labor of which 12 were concomitant with IUGR (25%). Six early pregnancy losses were recorded; there were 3 fetal deaths and 3 cases of pre-eclampsia/eclampsia. Conclusions LMWHs are used extensively during pregnancy and puerperium in Greece for VTE treatment and prophylaxis and for a variety of other indications as well. Although the drug has been shown to be both safe and efficacious, its use for some indications has no proven scientific evidence. In order to clearly define the role of LMWHs in pregnancy, beyond thromboprophylaxis, large prospective studies are required, which could be based on the conclusions of this study.

scholarly journals Antihyperlipidemic Effect of Seeds of Jamun (Eugenia jambolana) in Subjects of Intermediate Hyperglycemia: A Pilot Study

2021 ◽  
Author(s):  
Shagufta Parveen ◽  
Asim Ali Khan ◽  
Qamar Alam Khan
Keyword(s):  
Lipid Profile ◽  
Total Cholesterol Level ◽  
Vascular Complications ◽  
Substantial Effect ◽  
P Value ◽  
Glucose Levels ◽  
Eugenia Jambolana ◽  
Blood Glucose Levels ◽  
Group A ◽  
Group B

Intermediate hyperglycemia (Prediabetes) is a type of metabolic disorder with slight increase in the blood glucose levels from the normal but not reaching up to the level of diabetes. It is associated with many micro-vascular as well as macro-vascular complications. Abundance of Unani medicines are known for anti-hyperlipidemic activity, among them is Maghz-e-Jamun (Eugenia jambolana). The present study was to evaluate the anti-hyperlipidemic effect of Maghz-e-Jamun (Eugenia jambolana) in intermediate hyperglycemia. Patients diagnosed with prediabetes as per ADA criteria were randomly divided in two groups- group A was supplemented with 4.5g powder /day jamun seed powder in the form of capsules and group B was given placebo capsules. Lipid profile assessment was done at baseline and end of the treatment i.e., 84th day. There is considerable improvement in the lipid profile of the prediabetic subjects enrolled in the study especially significant improvement in total cholesterol level (from 266.47 ± 62.92 to 216.058 ± 40.14 with p value of 0.008**) and LDL (from 189.23 ± 55.07 to 138.58 ± 34.86 with p value of 0.003**). -Maghz-e-Jamun (Eugenia jambolana) show substantial effect on dyslipidemia in the patients of intermediate hyperglycemia.

Microscope-Study on the Relationship between Islet Cell Antibody and Cell Function in Children with Diabetes Mellitus

2021 ◽  
Vol 7 (5) ◽  
pp. 2938-2945
Author(s):  
Xinxia Zhang ◽  
Kunpeng Xu ◽  
Na Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Blood Glucose ◽  
Glucose Level ◽  
Islet Cell ◽  
Cell Function ◽  
Glucose Levels ◽  
Group A ◽  
Group B ◽  
The Relationship

The purpose of this study was to investigate the relationship between islet cell antibodies and cell function in children with diabetes mellitus. Objective: To investigate the effects of insulin resistance and B-cell failure on blood glucose levels in children with diabetes, so as to provide theoretical basis for rational choice of hypoglycemic drugs and effective control of blood glucose. Methods: 81 children with diabetes mellitus were tested after eating 80g instant noodles for 0, 30, 60,120 min of blood glucose and insulin. All cases were divided into group A (FPG < 8.92mmol /L) and group B (FPG≥ 8.89mmol /L) according to the fasting blood glucose (FFG) level. The contribution of cell function and insulin resistance to the blood glucose level was assessed in both groups. Results: The sensitivity of insulin and true insulin in group B was 65.5% and 64% of that in group A. After adjusting the effect of insulin resistance, the cell function in group B was only 1/5-1/7 of that in group A. Insulin swabs and cell function, measured by insulin, contributed half to glucose levels in group A, while cell function contributed eight times as much to glucose levels as insulin resistance in group B. Beta cell secretory function, measured with true insulin, explained 43% of the change in blood glucose in group A, 55% of the change in blood glucose in group B, and insulin sensitivity explained 13% of the change in group A, and 5.9% of the change in group B. Conclusion: Insulin resistance and cell failure were more serious in the group with higher fasting glucose level (≥ 8.89mmol /L), and the hyperglycemia was mainly caused by cell failure, suggesting that the combination of insulin sensitizer and insulin secretory agent was beneficial in the initial treatment.

Regulations of Free Fatty Acids and Diabetic Parameters in Drug Naïve Subjects with Type 2 Diabetes Treated with Canagliflozin Monotherapy

Drug Research ◽  
2021 ◽  
Author(s):  
Eiji Kutoh ◽  
Alexandra N. Kuto ◽  
Askuka Wada ◽  
Rumi Kurihara ◽  
Rina Kojima
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Beta Cell Function ◽  
Cell Function ◽  
Metabolic Parameters ◽  
Whole Body ◽  
Group A ◽  
Drug Naïve ◽  
Group B

AbstractThe objective of this study is to investigate the regulations of FFA with canagliflozin in relation to metabolic parameters. Drug naïve subjects with T2DM were administered 50–100 mg/day canagliflozin monotherapy (n=70) for 3 months. Significant correlations between the changes of (Δ) FFA and Δadipo-IR (R=0.496), but no correlations between ΔFFA and ΔHOMA-R were observed. The subjects were divided into three groups with similar numbers according to Δ FFA: group A: highest tertile: (ΔFFA=38.7%, n=23); group B: intermediate tertile: (ΔFFA=2%, n=23); group C: lowest tertile: (ΔFFA=−36%, n=24). Metabolic parameters were compared between group A and group C. At baseline, FFA was higher in group C than group A (p<0.002). Greater degrees of HbA1c reduction and increases of insulin were observed in group C than group A (both p<0.05). In group A, significant reductions of BMI (−2.6%) and HOMA-R (−30%) were seen. In group C, significant reductions of non-HDL-C (−6.2%), UA (−7.6%) or adipo-IR (−28.7%), and increases of HOMA-B (+85.6%) were observed. Taken together, 1) certain population treated with canagliflozin showed decreased FFA. 2) beta-cell function increased while atherogenic cholesterol, UA and adipo-IR decreased in those with reduced FFA. Better glycemic efficacies were seen in these populations. 3) body weight and whole body insulin resistance (HOMA-R) significantly decreased in those with elevated FFA. 4) FFA is linked to adipose insulin resistance (adipo-IR), while it does not appear to impact whole body insulin resistance (HOMA-R).

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