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Intra and Inter Laboratories results can differ due to variation in the experimental factors such as the protocol used, housing, temperature, light/dark cycle and the duration of study.

The techniques used in the lab can also introduce changes in metabolic regulatory pathways that are unaccounted. Studies have shown that use of anesthetics on organisms during study can affect the glucose metabolism by inhibiting the insulin response to glucose. This is also consistent with use of anesthetics in humans prior to surgeries, which is why anesthesiologist take extra precautions in dealing with diabetic patients. Laboratories temperature which are usually (18-22 °C) are lower than the thermoneutrality of the model organism which are about 30 °C. That can introduce hyperphagia in the organism to increase their metabolism in effort to generate heat energy for the body. This level of thermal stress can also have unaccounted effects on the organism.

Furthermore the spatial confinements can affect the brain chemistry in the social creatures like mice and rats making them more vulnerable to slower brain development and abnormalities due to the lack of social interactions. The psychological effects can introduce further discrepancy in the studies that makes it difficult to render proper data and hinders the possibility of recapitulating such experiments in humans. Rodents are nocturnal and are mostly feeding at night in their natural habitat. The changes in the light/dark cycle of laboratories can alter their circadian rhythm which can affect their metabolism. Besides that several studies used genetically modified mouse models that have decreased circadian rhythmicity gene. These cases have resulted in the increase of metabolic syndrome in the mouse models as well as resulted in obesity. The change in the phenotype can be a result of genetic modification of circadian clock gene, HFD, disruption of the circadian cycle by changes in light and dark cycle or can be due to the combination of all the factors. In order to find the exact cause requires further research. The cause of Diabetes mellitus type 2 (T2D) in humans are far more complicated than the solely the consumption of High Fat Diet (HFD). The mental, emotional and cultural factors along with insulin resistance and hyperphagia are known to increase the occurence of T2D in humans. However, T2D in model organisms are introduced via surgery of partial/ whole pancreas, or using chemicals such as Streptozotocin. Streptozotocin inhibits the ability of pancreatic β cells to produce insulin, and depending on the dosage used, the result can be partial or absolute inhibition. It can also interfere with other cell signalling pathways as well as affects the content of certain isozymes in organs like liver, brain and kidneys.