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Type 2 diabetes (T2D) is a heterogeneous disease with a multifactorial aetiology involving defects in the pancreatic beta cells, liver, muscles, adipose tissue, guts, brain, kidneys and heart. While genetics may only explain a minor proportion of T2D, the contribution of an adverse intrauterine environment may take centre stage in the global propagation of T2D. Impaired expandability of subcutaneous adipose tissue in persons with low birthweight may cause T2D due to lipotoxicity in non-adipose organs. Future implications include a stronger focus on individualized treatments in T2D patients and prevention of T2D in the next generations.

This article reviews the current evidence of effects on cardiovascular disease (CVD) of anti-diabetic treatment which exert their effect by increasing the insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, it has been demonstrated that metformin reduces the CVD risk. The effect of glitazones on CVD is uncertain. There is insufficient evidence to support a protective effect on CVD of lowering blood-glucose per se. In contrast, lowering blood glucose appears to decrease the risk of microvascular complications.

Significant progress in our understanding of age-related diseases including the metabolic syndrome, type 2 diabetes, arteriosclerosis and cancer have been achieved in recent years. Novel disease-causing mechanisms and, therefore, drug targets, include epigenetics, inflammation, telomeres, mitochondrial function, oxidative stress and sirtuins. There is a need for individualized treatments, and future medical interventions may be initiated in a primary preventive setting by targeting mechanisms similar to those influenced by calorie restriction and physical exercise.

Interleukin-1 receptor antagonist (IL-1Ra) expression is reduced in islets of patients with type 2 diabetes. 70 patients with type 2 diabetes were randomized to treatment with anakinra (IL-1Ra) or placebo for 13 weeks. Following treatment glycated hemoglobin was 0.46 percent lower, C-peptide secretion was enhanced, and systemic IL-6 and C-reactive protein levels were reduced in the anakinra group compared to the placebo group. Insulin resistance remained unchanged. Blocking IL-1 activity improved glycemia and b-cell secretory function and reduced markers of systemic inflammation.

A sedentary lifestyle, in conjunction with excessive food intake, is contributing to the worldwide increasing prevalence of obesity. Overeating is associated with insulin resistance, hypertension, dyslipoproteinaemia and endothelial dysfunction. A complicated network of cellular mechanisms has recently been suggested to play a central role in the control of energy homeostasis and metabolic response to overfeeding in animals. Understanding these mechanisms will substantially increase our knowledge about the physiological and biochemical factors leading to obesity and insulin resistance in humans.