Type 2 Diabetes Pathophysiology:
These genetic variations likely act together with health and lifestyle factors to influence your overall risk of T2D. Your lifetime risk of developing T2D is 40% if you have one biological parent with T2D and 70% if both of your biological parents have it. Type 2 diabetes used to be known as adult-onset diabetes, but both type 1 and type 2 diabetes can begin during childhood and adulthood. But the increase in the number of children with obesity has led to more cases of type 2 diabetes in younger people. The pancreas does not produce enough insulin ‘ a hormone that regulates the movement of sugar into the cells.
This secondary phenomenon, termed desensitization or ‘-cell glucotoxicity, is the result of a paradoxical inhibitory effect of glucose upon insulin release and may be attributable to the accumulation of glycogen within the ‘-cell as a result of sustained hyperglycemia (23). Other candidates that have been proposed are sorbital accumulation in the ‘-cell or the nonenzymatic glycation of’ -cell proteins. Availability of TGs within hepatocytes is important for VLDL synthesis [206] and the liver uses both de novo synthesized FAs and extra-hepatic FFAs as a substrate for TG synthesis [207]. De novo lipogenesis occurs primarily in the fed state in which the expression of lipogenic genes is regulated by the sterol regulatory element-binding protein (SREBP). The SREBP-1c isoform up-regulates almost all the enzymes involved in FA synthesis as well as enzymes that supply acetyl-CoA units and reducing equivalents to the pathway [208]. Insulin regulates SREBP-1c, which explains the lipogenic effect of chronic hyperinsulinemia [208].
Glucose tolerance and insulin-stimulated glucose uptake are also enhanced by resistive training, which increases total muscle mass without influencing glucose uptake per unit muscle mass (63). It is unknown whether these effects might differ between Indian people and Chinese people186,200. Although SGLT2 inhibitors are widely recommended among Asian populations203,204,205, data on the real-world use of SGLT2 inhibitors in China and India are scarce.
Targets of glucose control should be adapted to life expectancy, frailty, biological age, and social situation rather than just calendar age. HbA1c targets in this population need to be adjusted when using agents that cause side effects such as hypoglycemia. However, overt hyperglycemia needs to be addressed to avoid acute complications of diabetes and a catabolic state (141). Insulin secretion additional reading decline during the first few years after diagnosis has been described as biphasic, steeper during the first year than during the second year after diagnosis. The loss of insulin secretion can continue for years after diagnosis until little or no insulin secretion remains. However, low levels of C-peptide are detectable in the majority of patients after 30 years of type 1 diabetes (79).
This limitation in efficacy may be due in part to the fact that these agents are often initiated after ‘-cell function or mass has deteriorated beyond a critical level or to their limited effects on insulin secretion. Both long-acting and short-acting insulin analog preparations with more predictable time-action profiles have been developed, allowing patients to achieve more physiological insulin delivery and, therefore, tighter glucose control with fewer side effects. Technologies for self-monitoring blood glucose and continuous glucose monitoring have advanced in recent years and are becoming more widespread. Continuous glucose monitoring allows patients to visualize changes in glucose levels and tailor their treatment in real time (124). The amylin analog pramlintide is approved for use as an adjunct to insulin in patients with type 1 diabetes who have not achieved glycemic goals despite optimized insulin therapy. Pramlintide lowers postprandial glucose (125), thereby improving overall glycemic control, and it has a modest but significant weight loss effect.
Furthermore, inexpensive specific and sensitive assays to identify ‘-cell autoimmunity are needed, to be deployed on a population-wide level and beyond the confines of specialized laboratories. Fat may also accumulate in the pancreas and contribute to the decline in ‘-cell function, islet inflammation, and eventual ‘-cell death (61). Type 2 diabetes occurs at different levels of BMI/body fat composition in different individuals and at lower BMI for Asians additional reading and Asian Americans (62). For susceptible people, there may be a personal ‘fat threshold’ at which ectopic fat accumulation occurs, worsening insulin resistance and resulting in ‘-cell decompensation. Type 2 diabetes develops when ‘-cells fail to secrete sufficient insulin to keep up with demand, usually in the context of increased insulin resistance. A minority of people diagnosed with type 2 diabetes also have evidence of islet autoimmunity (57,58).
Afterwards, proinsulin is translocated from the ER to the Golgi apparatus (GA), entering into immature secretory vesicles and being cleaved into C-peptide and insulin [38,39]. In rare cases of uncontrolled diabetes, cats may experience damage to the nerves in the hind limbs, resulting in a ‘plantigrade’ stance of the hind limbs (walking or standing with their hocks on or close to the ground). The content on this page is for informational and educational purposes only and should not be relied on as medical advice. This information is not intended to be a substitute for professional medical advice, evaluation, or treatment of a qualified health-care provider. Always seek the guidance of your doctor or other qualified health professional with any questions you may have regarding your health or a medical condition, or if you are seeking medical advice, diagnoses, or treatment.
The incidence of diarrhoea as an adverse effect might be less common in Asian people than people who are not Asian163. This finding may be most applicable to east Asian people because the Asian populations included within this meta-analysis were predominantly east Asian. In a trial among Chinese people with coronary artery disease and IGT, acarbose prevented the onset of diabetes mellitus but did not reduce the frequency of cardiovascular events164. Insulin resistance and impairments in insulin secretion are crucial factors in the pathophysiology of T2DM26,27 (Box 2).
Mild age-related diabetes mellitus featured much higher HOMA-‘ and HOMA-IR among Indian people, but was otherwise generally similar to that seen in Chinese people110,111,112,114. Though there is no cure for feline diabetes, the prognosis for a good quality of life is good with adequate management at home. With early, aggressive treatment of diabetes, many cats will enter a state of diabetic remission, meaning they are able to maintain normal blood sugar levels without insulin injections. Older cats, cats who have previously received steroid medications, and cats treated with glargine insulin have been shown to be more likely to go into diabetic remission, but the most important factor is starting insulin therapy early and monitoring closely. If a cat has not entered diabetic remission within the first six months after diagnosis, it will almost certainly require life-long insulin injections.
These abnormalities lead to enhanced vasoconstriction, development of atherosclerosis, and favored thrombus formation [179,180]. The generation of ROS is highly implicated in the relationship between mitochondrial dysfunction and insulin resistance. ROS production takes place mainly at complex I and complex III of the ETC and increases when ETC is not able to handle excessive electron input. In these circumstances, as a consequence of nutrient overload, electron supply to the mitochondrial ETC increases and the electron excess is transferred to oxygen generating O2- and subsequent hydrogen peroxide [127]. ROS generated in mitochondria oxidize the Cys and Met residues in proteins, damaging protein structure, impairing their function and eventually causing cell death.
Hence the OLETF rats are proposed to be an experimental animal model for the study of mechanism of alteration of heart function [162]. STZ induced type 1 diabetes in spontaneously hypertensive rats (SHR rats) in over term develops myocardial damage characterized by fibrosis and apoptosis. Reduction of proinflammatory factors and reduced expression of antioxidant molecules are found to be responsible for the mechanism behind via the damage [163]. With such mechanisms, the STZ induced diabetes models are also used in the study of cardiomyopathy. Untreated GK rats induced with diabetes showed hyperglycemia, hyperlipidaemia and finally cardiac cell death in its progressive stage and hence are also employed in the study of diabetic cardiomyopathy [164]. Nearly half of all adults with type 2 diabetes mellitus (T2DM) live in India and China.