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Global Translational Medicine Keto diet in management of Type 2 diabetes

insulin deficiency occurs only when the pancreas is unable As previously noted, insulin secretion must always
to produce appropriate insulin, or the supplied insulin is adapt to meet oxygen demands. A diminished insulin
not adequately used by the body’s tissues and organs. There response in any of these tissues commonly enhances
are three main types of diabetes mellitus . overall IR, ultimately contributing to T2DM. IR and
[42]
Type 1 diabetes mellitus (T1DM), Type 2 diabetes pancreatic-cell failure occur simultaneously for the onset
[53]
mellitus (T2DM), and gestational diabetes are among the of T2DM . Individuals who are overweight or obese may
exhibit a certain level of IR, whereas diabetes generally
diverse subtypes of diabetes. Individuals with T1DM are manifests in those with reduced insulin emission relative
not generally obese, yet they still have a chance to develop to the levels of IR. However, insulin levels may indeed be
complications of diabetic ketoacidosis . A body mass
[43]
index (BMI) greater than 30 kg/m is an important point excessive in some individuals; controlling glycemic is not
2
in T2DM and is correlated with the development of IR always sufficient.
[44]
in physiological problems . Although obesity appears Obesity and T2DM have emerged as significant health
[44]
to promote T2DM and IR, the specific mechanism is challenges, driven by increasing screen time, reduced
unexplained. The physiology of this disorder is characterized physical activity, excessive calorie consumption, and the
by a mechanical failure in the feedback effects in between the consumption of sugary meals. The FDA has approved
proper functioning of insulin or insulin ejection, resulting sodium-glucose cotransporter 2 (SGLT2) inhibitors for
[54]
in fatigue and exhaustion in hyperglycemia . Metabolic managing the side effects of diabetes mellitus . While
[45]
derangement promotes T2DM by promoting both β-cell pharmaceuticals play a prominent role in treating T2D,
destruction and IR . The pathogenesis of β-cells may be post-marketing investigations have revealed adverse
[46]
associated with cell apoptosis . effects, including ketoacidosis, vaginal and urinary bladder
[47]
infections, malignancies, bone disease, and foot and ankle
Being overweight, leading to increased blood sugar [55]
and high cholesterol, consequently fosters long-term amputations .
inflammation in the body and IR. The cytoplasmic As a result, adopting a well-balanced diet and engaging
membrane, inflammation, the respiratory tract, and in strength training to promote weight loss and reduce
amyloid stress are among the perilous conditions to adiposity represent promising strategies to prevent or delay
which cells are exposed as a result of differences in their the onset of T2DM in individuals with slightly elevated
[56]
responsiveness to genomes. This leads pancreatic cells to risks . The American Diabetes Association (ADA) has
lose their adhesion . Subsequently, this triggers suicidal also recommended dietary counseling as a key component
[48]
[57]
unfolded protein response (UPR) systems, resulting in an of the overall management of individuals with T2DM .
oversupply of free fatty acids (FFAs), hyperglycemia, and Low-carbohydrate, high-fat regimens have become widely
cell malfunctioning by amplifying endoplasmic reticulum embraced among individuals with obesity and diabetes,
[58]
(ER) stress . In addition, obesity-related clinical disorders, based on contemporary controlled trials . Numerous
[49]
lipotoxicity, and glucolipotoxicity induce reactive, albeit researchers have discovered that KD plays a vital role in
detrimental, and energy metabolism stress, resulting in glycemic control and weight loss, proving to be an effective
the destabilization of β-cell . This cascade results in a strategy for both obese and diabetic patients [58,59] .
[50]
reduction of Ca ATPase in the Sarco/ER (SERCA), which
2+
is essential for transporting ER Ca ; the IP3 signaling 7. Result and discussion
2+
pathway and a unique breakdown of ER homeostasis can 7.1. Mechanisms linking obesity and diabetes
trigger the same UPR pathway when large amounts of Being overweight is linked to a wide range of clinical,
absorbed FFAs are detected .
[51]
sociological, and psychological issues. Furthermore, IR
Persistently elevated blood sugar, on the other hand, has been correlated with both T2DM and obesity. The
induces the elevation of islet amyloid polypeptides association between obesity and T2DM involves numerous
(IAAP) and catalyzes their reversible synthesis in β-cells. pathways, with adipocyte accumulation being one of the
This induction results in IAAP with insulin misfolding determinants of this physiological syndrome. In addition
accumulation and an enhancement in the establishment to IR, a significant portion of overweight individuals do
of reactive oxygen (ROS)-triggered oxidized protein not exhibit hypoglycemia. Under normal physiological
degradation components . These processes collectively conditions, pancreatic β-cells within the islet of Langerhans
[52]
damage ER, Ca transport, pro-apoptotic signals, cleavage secrete insulin adequately to counteract deficiency and
2+
of glucose transport mRNA, and the development of maintain normal blood sugar sensitivity . Mitochondrial
[60]
interleukin-1 (IL-1), which is also supported by monocytes dysfunction has been strongly associated with obesity or IR
and reduces inflammation in proximal islets . in both diabetes and pre-diabetic conditions, even among
[24]
Volume 2 Issue 4 (2023) 7 https://doi.org/10.36922/gtm.1361