A 55-year-old obese woman complains of declining visual acuity. Funduscopic examination shows peripheral retinal microaneurysms. Urinalysis reveals 3+ proteinuria and 3+ glucosuria. Serum albumin is 3 g/dL, and serum cholesterol is 350 mg/dL. These clinicopathologic findings are best explained by which of the following mechanisms of disease?

- Given clinical features point towards nephropathy & retinopathy resulted as complication of type-2 DM - Type-2 diabetes mellitus results from complex interplay b/w Underlying insulin resistance in its metabolic target tissues (liver, skeletal muscle & adipose tissue) & Reduction in glucose-stimulated insulin secretion, which fails to compensate for increased demand for insulin. - In obese persons, release of inhibitory mediators from adipose tissue interferes with intracellular signaling by insulin. - Hyperinsulinemia secondary to insulin resistance also downregulates number of insulin receptors on plasma membrane. Other choices are not related to pathogenesis of type 2 diabetes.