Gender dependent differences in lipid metabolism in individuals with type 2 diabetes mellitus.

AIM: The present study investigates gender dependent effects of insulin resistance on lipid profile and adipocytokines in individuals with diabetes receiving oral antidiabetic drugs (OADs). The aim was also to reveal the changes in the expression of genes involved in lipid metabolism and inflammation. METHODS: Lipid profile, adipocytokine levels and homeostatic model assessment of insulin resistance (HOMA-IR) was assessed in 100 patients with diabetes (M = 43, F = 57) matched for age and gender with healthy individuals (M = 45, F = 55). The expression pattern of genes was analyzed by quantitative real time PCR. RESULTS: Males consuming metformin with other drugs exhibited a positive association between HOMA-IR and cholesterol, triglyceride and very low density lipoprotein (VLDL). Females consuming only metformin and metformin with other drugs, showed a positive association of HOMA-IR with cholesterol and a negative association with adiponectin. In males and females with diabetes, a comparable expression of peroxisome proliferator activated receptor γ (PPARγ) while higher expression of sterol regulatory element binding protein 1 (SREBP1) was observed. Expression of fatty acid synthase (FAS), long chain acyl CoA Synthetases (ACSL), malonyl-CoA-acyl carrier protein transacylase (MCAT) and nuclear factor kappa ß (NFkß) was higher in men with diabetes than healthy males. Expression of tumor necrosis factor α (TNF-α) was higher in males and females with diabetes than respective healthy genders. CONCLUSION: Insulin resistance adversely affects lipid profile, adipocytokines in males with type 2 diabetes. Expression of genes involved in lipid metabolism and inflammation is found to be undesirably and differentially altered in both the genders.

High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκß, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.

Correlation of Serum Adiponectin and Leptin levels in Obesity and Type 2 Diabetes Mellitus.

INTRODUCTION: Indian phenotype includes higher waist circumference despite lower body mass index, thereby making Indians more prone to diabetes and its complications. AIM: The present study aimed to analyze the serum levels of adiponectin and leptin in the participants with type 2 diabetes mellitus (T2DM) and obesity and their correlation with hypertension and dyslipidemia. MATERIALS AND METHODS: In the study, 50 diabetics and 50 controls aged between 40 and 60 years were included in the study. RESULTS: Adiponectin levels were significantly higher in diabetics than in nondiabetic participants irrespective of gender (P ≤ 0.04 in males, P ≤ 0.02 in females). Leptin levels were significantly higher in diabetics compared to nondiabetics (P ≤ 0.001) in both males and females. CONCLUSION: Adiponectin and leptin levels may be used as important clinical markers for T2DM and obesity.

Adiponectin: A potential therapeutic target for metabolic syndrome.

Adiponectin is an important adipocytokine secreted chiefly by fat containing adipocytes, and plays a crucial role in glucose and lipid metabolism, inflammation and oxidative stress. Alterations in adiponectin levels have been shown to directly affect lipid and glucose metabolism that further increase the synthesis of lipids, free fatty acids and inflammatory cytokines. Changes in adiponectin levels also contribute to insulin resistance, obesity, cardiovascular diseases and type 2 diabetes. In the present review, we provide a comprehensive evaluation of the role of adiponectin and its molecular mechanisms in metabolic syndrome. Clinical improvement in adiponectin levels have been shown to positively modulate lipid and glucose metabolism, thus further substantiating its role in regulation of lipid and glucose metabolism. Currently adiponectin is being investigated as a potential therapeutic target for metabolic syndrome, although more research is required to understand the underlying mechanisms controlling adiponectin levels, including dietary and lifestyle interventions, that may target adiponectin as a therapeutic intervention in metabolic syndrome.

Gender dependent effects of fasting blood glucose levels and disease duration on biochemical markers in type 2 diabetics: A pilot study.

AIM: The impact of fasting blood glucose levels (FBG) and disease duration on type 2 diabetes in Indian population is still unclear. The present study examines gender-dependent effects of FBG and disease duration on lipid profile, adipocytokines and related biochemical parameters in diabetic individuals. METHODS: Type 2 diabetic individuals (n=100) were classified depending on FBG: patients with normal FBG (Glucose<126mg/dl) and patients with high FBG (Glucose≥126mg/dl); and disease duration: ≥0-≤3yr, >3-≤7yr, >7yr. RESULTS: Males with high FBG had significantly higher serum glucose, triglycerides, very low density lipoprotein (VLDL), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and waist hip ratio (WHR) than males with normal FBG. Females with high FBG had significant increase in serum glucose, adiponectin and creatinine while decrease in leptin levels than females with normal FBG. Males with high FBG had higher WHR, superoxide dismutase, SGOT, SGPT and lower adiponectin, leptin than females with high FBG. Significant positive association was observed between glucose and cholesterol, triglyceride, VLDL and urea in males with high FBG. With chronic diabetes for >7yr, males had increased systolic blood pressure, glucose, LDL, urea and low catalase activity as compared to other disease duration groups. However, females had higher adiponectin, creatinine and lower body mass index and cholesterol. CONCLUSIONS: High FBG in males adversely affects lipid profile, adipocytokines and liver function. Some of these effects exacerbate as disease progresses. Higher adiponectin may have desirable effects on metabolic markers in females.

Adipocytokines and anthropometric measures in type 2 diabetics.

AIM: Type 2 diabetes mellitus has assumed pandemic proportions worldwide. Aggressive management of hyperglycemia in diabetics is a primary goal of treatment. We have previously reported favorable effects of oral hypoglycemic agents on adipocytokines. Aim of the present study was to investigate the relationship of adipocytokines with anthropometric measures and biochemical parameters in type 2 diabetics. METHODS: Clinically diagnosed type 2 diabetics and age, gender matched healthy volunteers were recruited for study. Anthropometric measurements like height, weight, waist-circumference, hip-circumference were recorded and BMI, waist-hip ratio were calculated. Fasting blood samples were collected from participants and sera were analyzed for glucose, glycated haemoglobin, total cholesterol, SGOT, SGPT, insulin, adiponectin and leptin. Correlation of adipocytokines with anthropometric and biochemical parameters was assessed in healthy and diabetic individuals. RESULTS: BMI and WHR in diabetics were significantly higher than healthy population. BMI did not show significant association with adipocytokines. Diabetic males with WHR≥0.9 showed negative association with adiponectin and positive association with leptin. WC did not show significant association with adipocytokines in males. Irrespective of WC, healthy females exhibited positive association with leptin. Diabetic females with WC≥88cm showed leptin to be positively associated with WC. Such association of adipocytokines with WHR was not detected in females. CONCLUSIONS: Body fat distribution can be considered as a parameter in assessing adipokine imbalance. Central adiposity is a better measure of adipokine imbalance than BMI. Abdominal obesity in diabetics correlates with altered levels of adipocytokines indicating its importance in diabetic individuals.

Controversy of oral hypoglycemic agents in type 2 diabetes mellitus: Novel move towards combination therapies.

AIM: As diabetes mellitus is multi-factorial disease, use of several oral hypoglycemic agents (OHAs) is the main stay of pharmacological treatment. The treatment has become more challenging and controversial as OHAs are heterogeneous in their mode of action that causes unwanted side effects. Complementary approaches such as use of medicinal plants and dietary polyunsaturated fatty acids (PUFA) with hypoglycemic and hypolipidemic activities are therefore imperative. A vast literature has independently documented the effects of OHAs, medicinal plants and PUFA for management of diabetes. In the present article, we have reviewed the current literature to describe the effects of commonly used OHAs, their mechanisms of action and reported controversies. The antidiabetic potential of herbs and/or formulations and omega-3 PUFA with its potential benefits and mode of action is also discussed. METHODS: PUBMED, MEDLINE, Cochrane Library etc., were searched for relevant articles using appropriate terms (until February 2015). Human and animal studies were selected for the review. Data extraction was carried out by one author and checked by second author. RESULTS: There is still controversy over the safety profile of OHAs. Medicinal herbs with hypoglycemic activities are increasingly sought because of its natural origin, active constituents and minimal side effects. The current literature suggests that supplementation with PUFA improves macro- and microvascular complications. CONCLUSION: There is a need for best possible individualized treatment based on variations in biochemical parameters with combinational therapy of nutritional/herbal supplementations. Such a combination may be helpful for better management of diabetes and its complications.

Circulatory adipocytokines and lipid profile variations in type-2 diabetic subjects: desirable side-effects of antidiabetic drugs.

AIM: Inspite of availability of a variety of drugs to treat type 2 diabetes, little is known about their effects on other systems. Normalization of glucose metabolism by these drugs may consequently affect the secretory function in adipocytes. Secretory adipocytokines like adiponectin and leptin are emerging as novel therapeutic targets for type 2 diabetes mellitus (T2DM). The present study was undertaken to analyze the effects of commonly used Oral Hypoglycemic Agents (OHAs) alone, or in combination with other drugs and/or insulin on circulatory adiponectin and leptin levels, lipid profile, and blood pressure in diabetic subjects. METHODS: The study was undertaken at IRSHA and Bharati Vidyapeeth Medical College and Hospital, MS, India. Clinically diagnosed T2DM subjects and age, gender matched healthy controls were recruited. Fasting blood was collected from each subject and the blood samples were analyzed for circulatory adipocytokines and lipid parameters using commercial kits. RESULTS: Serum adiponectin levels were significantly increased while leptin significantly decreased in diabetic men (p<0.05) and women (p<0.001) on OHA, as compared to healthy controls. Triglyceride levels significantly decreased (p<0.05) in diabetic men, however, they remained unchanged in women despite same drug treatment. Serum HDL and LDL levels (p<0.001) were significantly lower in diabetic women as compared to healthy women. Systolic (p<0.05) and diastolic (p<0.001) blood pressure was significantly high in diabetic men but remained unchanged in women. CONCLUSIONS: Frequently used OHAs significantly improve circulatory levels of adipocytokines. Selecting best treatment option for each patient is a key, and 2012 European Association for the Study of Diabetes (EASD) and ADA guidelines recommend diabetes treatment to be individualized depending on various socioeconomic and lifestyle factors. We recommend regular analysis of circulatory adipocytokines in T2DM patients to help clinicians select the best treatment option to normalize levels of these important therapeutic targets.