The DIRECT study in the UK randomized 306 individuals with T2D (duration < 6 years, no insulin therapy, BMI 27–45 kg/m2) to usual care for T2D or intervention through caloric restriction (approximately 850 kcal/day) for 3–5 months using commercial formulas, followed by a gradual reintroduction of a conventional hypocaloric diet [64]. This evidence concerns the gene INS and type 2 diabetes mellitus.