R. Chetty

Insulin-Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone

Background—Obesity-associated hypertension is likely to be due to multiple mechanisms. Identification of the renin-angiotensin system (RAS) within adipose tissue does, however, suggest a potential causal role for it in obesity-associated hypertension. Obese patients are often hyperinsulinemic, but mechanisms underlying insulin upregulation of the RAS in adipose tissue are unclear. Tumor necrosis factor-α (TNF-α), an inducer of angiotensinogen in hepatocytes, is elevated in hyperinsulinemic, obese individuals and may provide a link in mediating insulin upregulation of the RAS in adipose tissue. Furthermore, thiazolidinediones lower blood pressure in vivo, and downregulation of the RAS in adipose tissue may contribute to this effect. We therefore examined the effect of rosiglitazone (RSG) on the insulin-mediated upregulation of the RAS. Methods and Results—Sera were obtained from the arterial circulation and from venous blood by draining subcutaneous abdominal adipose tissue. Isolated human abdominal subcutaneous adipocytes (n=12) were treated with insulin (1 to 1000 nmol/L), insulin in combination with RSG (10 nmol/L), and RSG (10 nmol/L) alone to determine angiotensinogen expression and angiotensin II, bradykinin, and TNF-α secretion. Subcutaneous adipocytes were also treated with TNF-α (10 to 100 ng/mL) to examine the direct effect on angiotensinogen expression and angiotensin II secretion. The findings showed that the arteriovenous difference in angiotensin II levels was significant (>23%; P<0.001). Insulin increased TNF-α secretion in a concentration-dependent manner (P<0.01), whereas RSG (10 nmol/L) significantly reduced the insulin-mediated rise in TNF-α (P<0.001), as well as angiotensin and angiotensin II. TNF-α also increased angiotensinogen and angiotensin II in isolated adipocytes. Conclusions—The present in vivo data suggest that human subcutaneous adipose tissue is a significant source of angiotensin II. This study also demonstrates a potential TNF-α–mediated mechanism through which insulin may stimulate the RAS and may contribute to explain obesity-associated hypertension. RSG downregulates the RAS in subcutaneous adipose tissue, and this effect may contribute to the long-term effect of RSG on blood pressure.

Association of simple anthropometric measures of obesity with visceral fat and the metabolic syndrome in male Caucasian and Indo-Asian subjects

Aims  The aims of this study were first, to investigate the relationship between simple anthropometric measures of obesity with visceral fat as assessed by a single slice magnetic resonance imaging (MRI)‐scan in patients attending a hospital clinic. Second, to determine which anthropometric measure best relates to the adverse metabolic profile of the metabolic syndrome.

Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol

Aims: Adiponectin is a 30‐kDa protein secreted by adipose tissue. The aim of the present study was to compare serum adiponectin in male Indo‐Asian and Caucasian subjects and examine its association with fat topography and metabolic parameters.

Serum resistin is associated with C-reactive protein and LDL- cholesterol in type 2 diabetes and coronary artery disease in a Saudi population

AimsResistin is an adipocyte-derived factor implicated in obesity-associated type 2 diabetes (T2DM). This study examines the association between human serum resistin, T2DM and coronary heart disease.MethodsOne hundred and fourteen Saudi Arabian patients (male: female ratio 46:68; age 51.4 (mean ± SD)11.7 years; median and range: 45.59 (11.7) years and BMI: 27.1 (mean ± SD) 8.1 Kgm2 median and range: 30.3 (6.3) were studied. Serum resistin and C-reactive protein (CRP), a marker of inflammation CRP levels, were measured in all subjects. (35 patients had type 2 diabetes mellitus (T2DM); 22 patients had coronary heart disease (CHD).ResultsSerum resistin levels were 1.2-fold higher in type 2 diabetes and 1.3-fold higher in CHD than in controls (p = 0.01). In addition, CRP was significantly increased in both T2DM and CHD patients (p = 0.007 and p = 0.002 respectively). The use of regression analysis also determined that serum resistin correlated with CRP levels (p = 0.04, R2 0.045).ConclusionThe findings from this study further implicate resistin as a circulating protein associated with T2DM and CHD. In addition this study also demonstrates an association between resistin and CRP, a marker of inflammation in type 2 diabetic patients.

MRI total sagittal abdominal diameter as a predictor of metabolic syndrome compared to visceral fat at L4–L5 level

ABSTRACT Objective: To compare associations between antero-posterior (AP) diameter or sagittal abdominal diameter – a measure of total central fat, and visceral fat alone with the metabolic syndrome as defined by ATPIII criteria. Research design and methods: Twenty-four Caucasian male with type 2 diabetes and 24 non-diabetic Caucasian male subjects [body mass index (BMI) (±SD): 32.23 ± 7.52 kg/m2, age (±SD): 51.35 ± 13.80 years] were studied by magnetic resonance imaging (MRI) scan to measure central fat at L4–L5 level. The visceral and total central adipose tissue was calculated in cm2 and total sagittal MRI diameter and visceral sagittal MRI diameters in cm. Components of the ATPIII definition of the metabolic syndrome and circulating adipocytokine concentrations were also measured. Results: MRI total sagittal abdominal diameter was positively associated with waist circumference in controls (r = 0.62, p = 0.007) and in diabetic subjects (r = 0.81, p < 0.001). Binary logistic regression analysis showed that MRI-calculated total sagittal diameter (r = 0.61, p = 0.002) was a more significant predictor of the adverse metabolic profile of the metabolic syndrome than MRI-assessed visceral fat. Receiver operating characteristic curves revealed that MRI-calculated total sagittal diameter most effectively identified subjects with the metabolic syndrome. Conclusions: MRI-calculated total sagittal abdominal diameter is a non-validated MRI method that predicts the adverse metabolic profile of the ATPIII definition of the metabolic syndrome. Antero-posterior fat is a dimension of central fat that seems to be more closely associated with cardiovascular risk compared to visceral fat.

The Management of Obesity in Type 2 Diabetes Mellitus

SUMMARY Prevalence of obesity in the United Kingdom has tripled in the last 20 years and this is driving an epidemic of type 2 diabetes. Indeed, today the vast majority of patients with type 2 diabetes are overweight or obese. Effective weight management leading to modest weight loss to the order of 5-10% of body weight can lead to significant clinically meaningful benefits provided it can be maintained. Thus weight management can lead to improved glycaemic control, better blood pressure control and lipid control in addition to other benefits. Management of diabetic patients who are obese requires management also of other associated co-morbid conditions and it is important to ensure that glycaemic control does not deteriorate during weight management. An integrated approach to weight management in the diabetic patient is recommended which helps to promote lifestyle modification for all patients. Drug therapy may be appropriate for many obese patients who do not reach target weight loss with lifestyle modification alone. Surgery should be reserved for those with BMI >40 only after failed medical therapy.