Current Management Strategies for Coexisting Diabetes Mellitus and Obesity

Abstract

Besides genetic predisposition, obesity is the most important risk factor for the development of diabetes mellitus. Weight reduction has been shown to markedly improve blood glucose control and vascular risk factors associated with insulin resistance in obese individuals with type 2 diabetes. Therapeutic strategies for the obese diabetic patient include: (i) promoting weight loss, through lifestyle modifications (low-calorie diet and exercise) and antiobesity drugs (orlistat, sibutramine, etc.); (ii) improving blood glucose control, through agents decreasing insulin resistance (metformin or thiazolidinediones, e.g. pioglitazone and rosiglitazone) or insulin needs (alpha-glucosidase inhibitors, e.g. acarbose) in preference to agents stimulating defective insulin secretion (sulphonylureas, meglitinide analogues); and (iii) treating common associated risk factors, such as arterial hypertension and dyslipidaemias, to improve cardiovascular prognosis. Whenever insulin is required by the obese diabetic patient after failure to respond to oral drugs, it should be preferably prescribed in combination with an oral agent, more particularly metformin or acarbose, or possibly a thiazolidinedione. When morbid obesity is present, both restoring a good glycaemic control and correcting associated risk factors can only be obtained through a marked and sustained weight loss. This objective justifies more aggressive weight reduction programmes, including very-low-calorie diets and bariatric surgery, but only within a multidisciplinary approach and long-term strategy.

Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes

“…Furthermore, improvement in glucose control results in decreased glucosuria and thereby limitation of energy wasting 8 . Thereby, losing weight and fat mass is challenging in patients with T2DM 7,19 .…”

“…The main clinical objectives in tackling the dual burden of obesity and T2DM may be : (i) in normoglycaemic overweight/obese patients, the primary prevention of T2DM, especially in patients at higher risk (those with impaired glucose tolerance for instance); (ii) in overweight/obese patients with T2DM, the reduction in bodyweight to facilitate glucose control (and reduce other risk factors) or at least avoid further weight gain; and (iii) the selection of effective treatments of both obesity and T2DM in the same patient while reducing associated CV risk factors and improving quality of life and life expectancy 19 . Similar to lifestyle changes, which positively influence both body weight and glucose control (Figure 2), other therapeutic interventions, especially pharmacological approaches, should ideally target both body weight and glucose regulation in an integrative approach 8,19 .…”

“…Similar to lifestyle changes, which positively influence both body weight and glucose control (Figure 2), other therapeutic interventions, especially pharmacological approaches, should ideally target both body weight and glucose regulation in an integrative approach 8,19 . However, long-term head-to-head comparisons of the various treatment options on overall patient's prognosis are still lacking for most approaches.…”

“…Blood glucose control becomes increasingly challenging in the obese patient with T2DM after failure of metformin monotherapy (a glucose-lowering medication that does not induce weight gain or hypoglycaemia) 11,19 . Attempts to reach fasting/postprandial glucose or glycated haemoglobin (HbA 1c ) targets with other therapies can lead to a higher risk of hypoglycaemia and/or weight gain, which can worsen overall prognosis 8 .…”

Cannabinoid-1 receptor antagonists in type-2 diabetes

“…[3][4][5] Yet individuals with type-2 diabetes often have more difficulty in losing weight and experience weight gain associated with most antidiabetic medications. 6,7 The treatment of multiple cardiovascular and metabolic riskfactors is central to the management of diabetic patients 1,2,5,8,9 , and the importance of weight management is well recognized in type-2 diabetes. 7,10,11 Over the last two decades a new biochemical/physiological system, known as the endocannabinoid (EC) system, was discovered.…”