Insulin resistance: Is it time for primary prevention?

Table 1 Pathologic changes associated with insulin resistance and compensatory hyperinsulinemia

Alterated glucose metabolism:

Impaired fasting glucose

Impaired glucose tolerance

Diabetes

Dyslipidemia:

↑ Triglycerides

↓ HDL-C

↑ Small, dense LDL-particles

Endothelial dysfunction:

↑ Adhesion molecules

↓ Endothelial-dependent vasodilation

↓ NO and ↑ ET-1 production

Hypercoagulability:

↑ Plasminogen activator inhibitor-I

↑ Fibrinogen

Hemodynamic changes:

↑ Sympathetic nervous system activity

↑ Renal sodium retention

↑ Cardiac mass

VSMC hypertrophy

Chronic inflammation:

↑ C-reactive protein, TNF-α, IL-6, resistin, leptin

↓ Adiponectin

↑ Oxidative stress

HDL-C: High density lipoprotein-cholesterol; LDL: Low density lipoprotein; NO: Nitric oxide; ET-1: Endothelin-1; VSMC: Vascular smooth muscle cells; TNF-α: Tumor necrosis factor-α; IL: Interleukin.

Table 2 Therapeutic approaches to insulin resistance

	Metformin	Thiazolidinediones	Berberine
Main mechanism of action:	Activation of AMPK	Activation of PPARγ	Activation of AMPK Up-regulation of insulin receptor expression Inhibition of intestinal disaccharidases
Metabolic effects:	Reduction in plasma FFA concentration Reduction in blood glucose, hemoglobin A1c, triglycerides, total and LDL-C, body weight and fat mass	Reduction in the amount of circulating FFA and in the lipolysis Improvement of hepatic production of glucose and insulin sensitivity	Reduction in plasma FFA concentration Reduction of blood glucose, hemoglobin A1c, total and LDL-C, triglycerides, body weight and fat mass
Side effects:	Abdominal discomfort, diarrhea and anorexia, lactic acidosis	Increase in total, LDL-C levels and body weight, hepatotoxicity, cardiotoxicity	Constipation

LDL-C: Low density lipoprotein-cholesterol; FFA: Free fatty acids; AMPK: AMP-activated protein kinase; PPAR: Peroxisome proliferator-activated receptors .