Obesity and Type 2 Diabetes Mellitus (T2D) are serious health concerns. In the next section, we discuss the association between obesity and T2D in more. Background The relationship between obesity and type 2 diabetes mellitus ( T2DM) varies with geographical area and race. Objectives To investigate the. The relationship between obesity and diabetes is of such interdependence that the term 'diabesity' has been coined. The passage from obesity to diabetes is.
Visceral fat content is an independent predictor of insulin resistance, whilst adipokines such as adiponectin protect against obesity-induced T2D.How Lipoproteins Affect Metabolism in Diabetes
Further study of the precise mechanisms of lipotoxicity in the development of T2D will enable development of novel strategies to manage and eventually prevent onset of T2D in the context of obesity.
In this brief review article, we discuss the currently-understood intricate associations between obesity and T2D and options for management. The global epidemic of obesity and T2D is worsening. T2D is closely associated with excessive body fat and physical inactivity [ 5 ]. It is predicted that there will be a growing burden of DM, and that the world prevalence of DM amongst adults aged years will increase to million by [ 8 ].
In the next section, we discuss the association between obesity and T2D in more detail. Health Technology Assessment systematic reviews showed that weight loss was beneficial for longterm T2D-related outcomes and risk of developing T2D in overweightobese and morbidly-obese participants [ 11 ]. Factors other than fat mass per se also influence risk of development of T2D. It is clear that fat distribution is relevant to the risk of developing T2D, with central visceral adiposity conferring the greatest risk.
Waist circumference, a useful clinical surrogate measure of visceral fatis a useful predictor for subsequent development of T2D.
Link between obesity and type 2 diabetes.
An increase in waist circumference is associated with an increase in the risk of developing T2D. In one study, age-adjusted ORs for development of T2D in overweight and obese men were reported as 2. More recently, Nguyen and colleagues explored the relationship between obesity and T2D in a US adult population based on findings from the National Health and Nutrition Examination Survey, — [ 14 ]: Amongst the 21, surveyed adults, 2, Amongst those with T2D, It is clear from the data presented above that BMI and particularly visceral adiposity are associated with the development of T2D.
There is also clear evidence that effective weight loss improves glycaemic control in adults with established T2D, and in certain cases for example following weight loss with bariatric surgery euglycaemia can be achieved. Clinically significant weight-loss at 1-year in T2D was associated with improved diabetes control [ 15 ].
Physiologically, glucose homeostasis is maintained by an intricate balance between insulin secretion from pancreatic beta-cells and insulin sensitivity of peripheral tissues, both of which are influenced by particularly visceral fat mass through effects of adipokines and lipotoxicity Figure 1. Our current understanding of Diabesity however does not explain the whole picture given that T2D can develop in lean adults, and not all obese adults develop T2D.
Further research is required to gain a clearer understanding of the pathogenesis of T2D and the complex mechanisms involved that fully explain how obesity and T2D are linked. In the following sub-sections, we outline some of the current main hypotheses regarding obesityrelated pathogenesis of T2D.
FFAs and ectopic fat in the development of obesity-related T2D Development of T2D is closely associated with both overall and abdominal adiposity, highlighting the importance of waist circumference measurement in clinical assessment [ 16 ]. Duration of abdominal obesity is also associated with risk for development of T2D independent of severity of abdominal adiposity [ 18 ].
These observations implicate central visceral adiposity as an important fat depot for T2D development. One hypothesis is that increased visceral fat results in greater amounts of FFAs reaching the liver via the portal vein resulting in fatty liver. This is associated with elevated non-esterified fatty acid NEFA levels in the plasma that in turn result in insulin resistance via Randle's effect in the peripheral insulin target tissues such as muscle [ 1920 ].
Obesity and Type 2 Diabetes Mellitus
This latter hypothesis views T2D as a state of chronic inflammation, and the beta-cell dysfunction and insulin resistance as manifestations of a broader systemic chronic inflammatory condition. At this point, fat deposition is diverted to extraadipose tissue sites such as liverskeletal muscle and the pancreatic insulin-secreting beta cell, resulting in worsening insulin resistance, impaired beta-cell function and ultimately T2D [ 21 - 24 ].
Ectopic fat deposition is believed to be the result of synergistic effects of increased dietary intakedecreased fat oxidation, and impaired adipogenesis beyond the critical visceral adipose tissue depot threshold [ 25 ]. Oxidative stress has been proposed to be a pathogenic mechanism underlying development of insulin resistance, T2D, obesity and cardiovascular disease [ 2627 ].
Excessive intracellular Reactive Oxygen Species activate multiple signalling cascades and kinases that ultimately result in inhibition of insulin action [ 26 ], mitochondrial damage and enhanced beta-cell apoptosis, all of which play important roles in the development of obesity-related T2D [ 26 - 28 ].
When this occurs, adipocytes release fatty acidsmediators of inflammation and various adipocytokines [ 2930 ].
Obesity and Type 2 Diabetes Mellitus | OMICS International
In response to diverse nutrient and neuro-hormonal signals, adipose tissue secretes adipocytokines that control feeding, thermogenesis, immunity, and neuroendocrine function [ 2930 ]. These adipocytokines serve to alter insulin sensitivity of various insulin-target organs, thereby contributing to pathogenesis of obesity-related T2D.
Important adipocytokines in this regard include leptin, adiponectin, resistin, and visfatin [ 29 - 32 ]. The mechanisms whereby each of these adipocytokines may mediate the development of T2D in obesity are outlined below. Elevated leptin levels signal satiety to the brain through receptors in hypothalamic and brainstem neurons.
Leptin increases levels of anorexigenic peptides, and inhibits orexigenic peptides.
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- Diabetes and Obesity
Leptin also has peripheral effects with leptin receptors having been observed in myocytes, liver and pancreas. Peripherally, leptin has been demonstrated to have beneficial effects on glucose metabolism and prevention of hyperglycaemia, and some of these effects are thought to be additive to those of insulin action [ 2930 ].
Furthermore, leptin stimulates fatty acid oxidation and insulin release, and enhances peripheral insulin action via regulation of the enzymesPhophatidylinositol 3 PI-3 kinase, suppressor of cytokine signaling-3 SOCS-3and AMP-activated protein kinase in the brain and peripheral tissues [ 31 ]. Adiponectin has been linked to glucose, lipid, and cardiometabolic regulation with potent insulin-mimetic, insulinsensitizing and anti-inflammatory properties [ 29 - 32 ].
Obesity, T2D and atherosclerosis are associated with reduced serum adiponectin levels. In obese and insulin-resistant states, receptors for adiponectin are also down-regulated, further reducing its beneficial effects. In obesity and insulin resistant states, reduced serum adiponectin levels are influenced by effects on adiponectin gene transcription, and repression of adiponectin production by tumour necrosis factor-alpha TNFalpha and Interleukin-6 IL-6 [ 293334 ].
Elevated serum levels of resistin in obesity results in an increase in the production of adipocyte-derived chemotactic agents and pro-inflammatory cytokines. These cytokines suppress hepatocyte Insulin Receptor Substrate-2 IRS-2 and uncouple the insulinsignalling pathway in hepatocytes [ 2935 - 38 ], thereby contributing towards hepatic insulin resistance. In skeletal myocytes, resistin also impairs glucose-uptake and blocks the insulin transduction pathway [ 38 ].
Through its effects on hepatocytes and myocytes, resistin is believed to play an important role in the development of T2D in obesity. Recent studies suggest that visfatin may represent a proinflammatory cytokine that is influenced by serum levels of insulin and degree of insulin resistance.
Link between obesity and type 2 diabetes.
In this way, visfatin may also play a role in the development of T2D in obesity [ 2939 ]. It is clear from the above discussion that there are many known adipocytokines that correlate with severity of obesity and degree of insulin resistance, and that probably play important roles in the development of T2D in obesity.
It is likely that further adipocytokines will be identified in future years that may add to the complexity of diabesity. It is also clear, however, that some of the mechanisms identified for various adipocytokines such as visfatin implicate inflammatory pathways.
Our view of diabesity in recent years has migrated towards that of a chronic inflammatory condition. Recent evidence implicates inflammatory pathways in the development of T2D in obesity.
This is discussed further in the next section. Inflammation in the development of obesity-related T2D Low-grade inflammation at the level of the adipocyte and systemically are characteristic of diabesity states. It is likely that inflammatory signals interfere with metabolic pathways at the cellular level, such effects including impairment of the insulin-signalling pathway in peripheral tissues.
In this way, it is thought that chronic inflammation may promote insulin resistance in obesity thereby contributing towards the development of T2D. Various molecules have been implicated in the chronic inflammation that characterises diabesity. These include pro-inflammatory cytokines derived from both the adipocyte and macrophages within adipose tissue [ 294041 ]. It is likely that these molecules play important roles in the development of T2D in obesity [ 40 - 45 ].
The intricate role of chronic inflammation in diabesity, how this interacts with the metabolome and metabolic pathways, and the mechanisms whereby chronic inflammation develops in obesity and insulin resistant states and the upstream triggers for this process are all areas of current and future research. Through developing a clearer and more complete understanding of these pathways and triggers, we will establish novel targets for therapies that are targeted towards key pathways in the development of diabesity, thereby potentially for use in the prevention and treatment of T2D in obese and insulin-resistant states.
Mean insulin and c-peptide levels were highest for diabetics with BMI equal to These results may suggest that more diabetics within normal weight range have type 1 classification and diabetes in the obese are mostly type 2 with associated insulin resistance.
The finding of a high prevalence of obesity in adults with diabetes from this study suggests that more effort should be taken to combat obesity since obesity is a modifiable risk factor for the development of diabetes. These efforts should include prevention of obesity in combination with medical and surgical treatments of obesity.
Participants randomized to lifestyle intervention lost an average of 8. A greater proportion of the individuals in the lifestyle intervention group had reduction in diabetes, hypertension, and lipid-lowering medications. The mean hemoglobin A1C level improved significantly more in the lifestyle intervention than control participants [ 11 ].
Bariatric surgery has also been shown to improve and even induce remission of diabetes in the morbidly obese. In a large study on patients with diabetes or have impaired fasting glucose levels, Schauer et al. In a meta-analysis of 19 studies and 11, patients on the effect of bariatric surgery on diabetes, Buchwald et al.
In addition to the findings of improvement of diabetes with bariatric surgery, several recent studies have shown improved survival rates for morbidly obese individuals who underwent bariatric surgery compared to the control individuals without surgical intervention [ 1415 ]. Lastly, prevention of obesity is a key public health initiative in an attempt to reduce the incidence of obesity and diabetes risk.
Currently, Head Start is the largest federally funded early childhood obesity education program in the United States.
In a survey of 1, Head Start programs, Whitaker and colleagues reported that most Head Start programs are doing more to support healthy eating and gross motor activity than required by federal requirement standards [ 17 ]. Our study shows a clear association between obesity and diabetes, using a large nationwide database.
However, there are notable limitations in the use and interpretation of this observational data. Therefore, longitudinal data across study years is not provided, and no temporal analyses can be conducted. As with all survey data, there are inherent limitations in the collection methods, which can lead to sampling error, measurement error, and reporting bias.
Conclusions In summary, our findings demonstrate an association between increasing obesity classes and increasing prevalence of diabetes. Nearly one fourth of adults with diabetes have poor glycemic control and nearly half of adult diabetics are considered obese based on an 8-year period — data from a cross-sectional representative of the US adult population.
An important implication from this study is that medical or surgical weight loss and obesity prevention are important interventions in an effort to reduce the impact of diabetes on the health care system. Acknowledgments Conflict of interest The authors declared that there are no conflicts of interest. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author s and source are credited.
Prevalence of diabetes and high risk for diabetes using hemoglobin A1c criteria in the U.