Tuesday, November 21, 2017

Fats role in Type 2 diabetes

It is known that people develop type 2 diabetes mellitus (T2DM) due to increased insulin
resistance and diminished pancreatic beta cells (b-cells) which produce insulin. When the
human body is unable to produce insulin to regulate blood glucose levels a person will
develop T2DM. Many factors play a role in developing T2DM; genetics, sugar consumption,
fat consumption, lack of exercise, weight status (BMI), and others. This paper looks at how
ingesting high fat diets, particularly diets high in saturated fat, can cause diabetes.
Insulin works by locking onto a cell wall which activates the inside of the cell to allow blood glucose to come in the cell and out of the blood stream. Increased insulin resistance occurs when insulin latches onto the cell and the mechanism inside the cell
fails to allow glucose into the cell. According to Bosma, M., Kersten, S., Hesselink, M.K.C., & Schrauwen, P., (2011) increased intramyocellular lipid (IMCL) levels, which are associated with obesity, negatively correlate with insulin sensitivity. This means
an accumulation of fat in the muscle is associated with a reduction in insulin mediated glucose uptake.
They go on to indicate that the mechanism for cell inhibition of uptake of blood glucose is still under investigation. There are possible connections to lipid intermediates. These intermediates somehow stop the signaling process once insulin attaches to
the cell. The enzymes which should activate to signal the glucose transporter never start their process. This leads to blood glucose being left outside the cell which elevates blood glucose levels.
Insulin resistance is half the problem when developing T2DM. Decline of b-cell function also contributes to the disease. It can start by a person consuming excess fat/calories, causing excess muscle fat buildup, which can lead to a decrease in pancreatic
function to release insulin. According to Taylor, R., (2013) fatty muscles happen when caloric intake is greater than expenditure. This results in a buildup of fat in the liver. As the amount of fat in the liver increases, insulin sensitivity in the liver decreases. Since a fatty liver can become deadly, the liver will try to release fat in the form of very low density lipoprotein (VLDL). The pancreatic islets are therefore exposed to increased levels of VLDL. People respond individually to different levels
of this fat exposure, but at a point the b-cells will fail to adequately respond, resulting in cell death and elevated blood glucose levels.
This pancreatic b-cells apoptosis is what can lead to T2DM becoming a lifelong disease. A study by Cnop, M., et al. (2010) concluded that people’s b-cells formation is largely established by age 20. This would imply that when the b-cells are destroyed by VLDL exposure, they are gone for the remaining lifespan of the person, decreasing the person’s ability to produce insulin to
decrease blood glucose levels. When discussing fat consumption, it is also important to determine whether it is all fat or certain fats that can lead to IMCL, insulin resistance, and b-cell loss. From in vitro studies described by Nolan, C.J., & Larter, C. Z., (2009) it is known that saturated
fatty acids (SFA) are toxic to cells while monounsaturated fatty acids (MUFA) are cytoprotective. Martins, A.R., et al., corroborates the connection that SFAs and trans fats are linked to increased insulin resistance. There are multiple theories about how SFAs effect insulin sensitivity. Some of these are SFAs alter gene expression, activation of inflammatory pathways, Rande cycle (competition between SFAs and glucose), SFAs inhibition of cell signaling, and impairment of the mitochondria.
Studies and discussions of these theories indicate that multiple processes contribute rather than a single mechanism.
SFAs and trans fat are most commonly found in animal products. When looking at the correlation between meat and T2DM The InterAct Consortium, (2012) found a positive association between high consumption of total and red meat and T2DM in a large cohort of European adults. Studies by Gojda, J., et al., (2013) and Goff, L.M., Bell, J.D., So, P-W., Dornhorst, A., & Frost, G.S.,
(2005) compared vegans to omnivores with the same BMI and activity level. They concluded that vegans had better insulin sensitivity, lower IMCL, better glucose hemeostasis, plasma lipid profile, less muscle lipids, and improved b-cell function. They conclude that eating less to no meat may help protect people from developing T2DM. Studies of chronic disease support that everyone, not only patients with T2DM, may benefit by reducing their fat intake, particularly saturated fat and trans fat, to ensure proper function of cells and vital organs to prevent chronic diseases from
progressing. Diet plays an important role in disease prevention and treatment. Boucher, Evert, Daly, Kulkarni, Rizzotto, Burton and Bradshaw (2011) state that the three pillars of diabetic treatment are nutrition, physical activity, and medication therapy and that the most important of these is a healthy diet.
Boucher, J. L., Evert, A., Daly, A., Kulkarni, K., Rizzotto, J., Burton, K., & Bradshaw, B. G. (2011). American Dietetic Association
revised Standards of Practice and Standards of Professional Performance for registered dietitians (generalist, specialty,
and advanced) in diabetes care. Journal of the American Dietetic Association, 111, 156-166. doi: 10.1016/
Bosma, M., Kersten, S., Hesselink, M.K.C., & Schrauwen, P., (2011). Re-evaluating lipotoxic triggers in skeletal muscle: Relating
intramyocellular lipid metabolism to insulin sensitivity. Progress in Lipid Research, 51, 36-49. Doi: 10.1016/
Cnop, M., Hughes. S.J., Igoillo-Esteve, M., Hoppa, M.B., Sayyed, F., Laar, L., … & Clark, A., (2010). The long lifespan and low
turnover of human islet beta cells estimated by mathematical modeling of lipofuscin accumulation. Diabetologia, 53,
321-330. Doi: 10.1007/s00125-009-1562-x
Goff, L.M., Bell, J.D., So, P-W., Dornhorst, A., & Frost, G.S., (2005). Veganism and its relationship with insulin resistance and
intramyocellular lipid. European Journal of Clinical Nutrition, 59, 291-298. Doi: 10.1038/sj.ejcn.1602076
Gojda, J., Patkova, J., Jacek, M., Potockova, J., Trnka, J., Krami, P., & Andel, M., (2013). Higher insulin sensitivity in vegans is not
associated with higher mitochondrial density. European Journal of Clinical Nutrition, 67, 1310-1315. Doi: 10.1038/
Martins, A.R., Nachbar, R.T., Gorjao, R., Vinolo, M.A., Festuccia, W.T., Lambertucci, F.H., … & Hirabara, S.M., (2012).
Mechanisms underlying skeletal muscl insulin resistance induced by fatty acids: importance of the mitochondrial
function. Lipids in Healht and Disease, 11, 30. Doi: 10.1186/1476-511X-11-30
Nolan, C.J., & Larter, C.Z., (2009). Lipotoxicity: Why do saturated fatty acids cause and monounsaturates protect against it?.
Journal of Gastroenterology and Hepatology, 24, 203-711. Doi: 10.1111/j.1440-1746.2009.05823.x
Taylor, R., (2013). Banting memorial lecture 2012 reversing the twin cycles of type 2 diabetes. Diabetic Medicine, 30, 267-275.
Doi: 10.1111/dme.12039
The InterAct Consortium, (2012). Association between dietary meat consumption and incident type 2 diabetes: The EPICInteraAct
study. Diabetologia, 56, 47-59. Doi: 10.1007/s00125-012-2718-7

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