TYPE 2 DIABETES

                                 THE TREATMENT OF METABOLIC ABNORMALITIES

    Abdominal obesity is associated with numerous metaolic abnormalities, including insulin resistance, impaired glucose
tolerance/type-2 diabetes, and atherogenic dyslipidaemia with low high-density lipoprotein (HDL) cholesterol, high triglycerides, and increased small dense low-density lipoprotein (LDL) cholesterol. A proportion of these metabolic disorders may be attributed to increased endocannabinoid activity. The selective cannabinoid 1 (CB1) receptor antagonist rimonabant has been shown to reduce boldy weight, waist circumference, insulin resistance, triglycerides, dense LDL, C-reactive protein (CRP), and blood pressure, and to increase HDL and adiponectin conecentrations in both non-diabetic and diabetic overweight/obse patients. Besides an improvement in glucose tolerance in non-diabetic subjects, a reduction of 0.5-0.7% in haemoglobin A1C (HbA(1c)) levels was consistently observed in vatious groups of patients with type-2 diabetes. Almost half the metabolic changes could not be explained by weight loss, supporting direct peripheral effects of rimonabant. Ongoing studies should demonstrate whether improved metabolic disorders with CB1 receptor antagonists (rimonabant, taranabant, etc.) would translate into fewer cardiovascular complications among high-risk individulas.

TYPE 2 DIABETES

                 RECEPTOR ANTAGONISTS CANNABINOID-1 IN DIABETES TYPE 2

     Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a risk of major cardiovascular disease. In human central and peripheral endocannabinoid actions, via the activation of Cb1 receptor, promote weight gain and associated metabolic changes. Rimonabant, the first selective CB (1) receptor blocker to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance index and C-reactive protein levels, and to increase high-density lipoprotein (HDL) cholesterol and adiponectin conecentrations in both non-diabetic and diabetic overweight/obse patients. A 0.5-0.7 % reduction in HbA1c levels was observed in metformin- or sulphonylurea-treated patients with type-2 diabetes and in drug-native diabetic patients. Almost half of the metabolic changes, including HbA1c reduction, could not be explained by weight loss, sugesting that there aredirect peripheral effects. Rimonabant was generally well-tolerated, and the safety profile was similar in diabetic and non-diabetic patients, with a higher incidence of depressed nood disorders, nausea and dizziness. The potential role of rimonabant in over weight/obse patients with type-2 diabetes and at hight risk of cardiovascular disease deserves much consideration

TYPE 2 DIABETES

    THE ADIPOSE-TISSUE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

    Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen form adipocyted. Angiotensin II acts as an antiadipogenic substance in human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increasedespecially inobse hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Although the mechanisms are still speculative, the beneficial effecs of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes. Suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.
     

TYPE

THE ADIPOSE-TISSUE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (ROLE IN THE                                             METABOLIC SYNDROME)

TYPE 2 DIABETES

                ADIPOSE-TISSUE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEMS


     

TYPE 2 DIABETES

  RELATIONSHIP BETWEEN CANNABINOID AND GLUCOSE METABOLISM
     
Cannabinoid 1 receptors have been identified not only in the brain, but also in the adipose tissue, the gut, the liver, the skeletal muscle and even the pancreas. all organs playing a key role in glucose metabolism and type 2 diabetes. Rimonabant, the first selective cannabinoid 1 receptor blocker being use to reduce body weight, waist circumference, glycated haemoglobin, triglycerides, insulin resistance index, and to increase HDL cholesterol and adiponectin concentrations in patients with type 2 diabetes, confirming data on nondiabetic overweight/obse patients. Almost half of the metabolic changes, including glycated haemoglobin reduction. could not be explained by weight loss, in agreement with direct peripheral effects.