Diabesity - 21st Century Pandemic, We are Still Fighting
Authored by Bijaya Mohanty
Abstract
The term diabesity was coined by Ethan Sims in 1973,
to describe the strong relationship between type 2 diabetes mellitus
(T2DM) and obesity. The risk of diabetes increases markedly as the BMI
increases over 25kg/m2. This 21st century pandemic
needs to be addressed on a war foot basis considering the economic
costs, social hazards, morbidity and mortality of the disease. Recent
studies have identified links between obesity and type 2 diabetes
involving pro-inflammatory cytokines (tumor necrosis factor and
interleukin-6), insulin resistance, deranged fatty acid metabolism and
cellular processes such as mitochondrial dysfunction and endoplasmic
reticulum stress. The influence of obesity on type 2 diabetes risk is
determined not only by the degree of obesity but also by where fat
accumulates (visceral vs subcutaneous). Emerging evidences suggests that
different subtypes of adipose tissue may be functionally distinct and
affect glucose homeostasis differentially. Factors predisposing to
p-cell depletion & degradation could also be primarily genetic or
epigenetic. Genome-wide association scans (GWAS) and candidate gene
approaches have identified over 40 genes associated with type 2diabetes
&obesity. Even some of the glucose lowering medications are
associated with weight gain, posing a challenge to physicians &
dialectologists.
Body weight with current therapeutic options needs
more consideration. This issue is particularly important because it has
been observed that even modest weight reduction-whether through
lifestyle modification, behavioral interventions, anti-obesity drugs, or
bariatric surgery can improve glycemic control and reduce diabetes
risk. Prevention and treatment of obesity will definitely improve the
incidence and care of type 2 diabetes patients. Holistic and
collaborative approach is the key to success in a diabesity clinic where
the team includes dialectologist, well trained nurse, dietitian,
physiotherapist psychologists & bariatric surgeon.
Abbreviations: GWAS:
Genome-Wide Association Scans; IDF: International Diabetes Federation;
CVD: Cardiovascular Disease; RYGB: Roux-En-Y Gastric Bypass;
Introduction
It has been twelve years since the theme of world
diabetes day - FIGHT OBESITY PREVENT DIABETES in the year 2004. Where do
we stand now? We are still fighting. The global prevalence of obesity
is increasing day by day. Excess weight is a worldwide phenomenon in
both male & female. It is projected to reach to almost 50% in some
countries. Diabesity (Diabetes type 2 & obesity) is the 21th century
pandemic. The International Diabetes Federation (IDF) 2014 has
projected that by the year 2035 approximately 592 million people will be
affected by this killer disease all over the world, out of which 90%
will have type 2 diabetes mellitus. This magnitude of the problem &
the gravity of the situation led to growing concern among the health
care professionals. This pandemic needs to be addressed aggressively
considering the economic burden, morbidity & mortality [1-5].
Diabetes & Obesity
The term diabesity was coined by Ethan Sims in 1973,
to describe the close relationship between diabetes mellitus type 2
(T2DM) and obesity. The risk of diabetes increases exponentially as the
BMI increases over 25kg/m2. The risk increases by 2 to 8 fold
at BMI of 25 and 10 to 40 fold when BMI is more than 30 and at BMI
greater than 35, the risk increases 40 fold depending on ethnicity, age,
sex, duration and degree of adiposity. Obesity is most commonly caused
by a combination of excessive food intake especially high calorie food,
lack of physical activity and genetic susceptibility. Excess weight is
an established risk factor for type 2 diabetes, yet most obese
individuals do not develop type 2 diabetes. However 90% of type 2
diabetics are overweight or obese. Recent studies have identified links
between obesity and type 2 diabetes involving pro-inflammatory cytokines
(tumor necrosis factor and interleukin-6), insulin resistance, deranged
fatty acid metabolism and cellular processes such as mitochondrial
dysfunction and endoplasmic reticulum stress [6-10].
These interactions are complex, with the relative
importance of each poorly understood. Further genetic studies may
elucidate additional common pathophysiological pathways for obesity and
diabetes and identify promising new treatment targets. These intriguing,
but still largely unexplored, connections between obesity and type 2
diabetes suggested the timely need to convene a group of scientific
experts in the fields to more closely examine underlying pathophysiology
and treatment options for patients with type 2 diabetes addressing
issues of excess weight and glycemic control simultaneously. The
influence of obesity on type 2 diabetes risk is determined by the
degree& type of obesity (Visceral/Subcutaneous). In truncal obesity
there is increased upper body fat including visceral adiposity reflected
by increased abdominal girth, increased waist-to-hip ratio, is
associated with the metabolic syndrome, type 2 diabetes, and
cardiovascular diseases. Whether, subcutaneous fat lacks the
pathological effects of visceral fat needs to be studied further [11-13].
Beyond differences in body fat distribution, emerging
evidence suggests that different subtypes of adipose tissue may be
functionally distinct and affect glucose homeostasis differentially.
Adult humans have limited and variable numbers of brown fat cells which
play a role in thermogenesis and potentially influence energy
expenditure and obesity susceptibility. Improved understanding of the
function of different fat cell types and depots and their roles in
metabolic homeostasis is a priority for investigation into the
pathogenesis of obesity. Likewise, adipose tissue is composed of
heterogeneous cell types. Immune cells within adipose tissue also likely
contribute to systemic metabolic processes. As the study of adipose
biology progresses, it will be important to consider whether additional
subtypes of adipocytes or other cell types can be identified to refine
our understanding of obesity complications and generate novel approaches
to prevention. Though the exact pathophysiology linking obesity with
type 2 diabetes is not yet established. There are several distinct
mechanisms that have been postulated which link obesity to insulin
resistance and predispose to type 2 diabetes. One school of thought
suggests macrophages infiltrate fat tissue and produce chemical
mediators called cytokines including tumor necrosis factor-α, resistin
and retinol-binding protein 4 leading to inflammation and insulin
resistance. In obese individuals the fat cells get enlarged and release a
specific chemical called chemerin and this chemerin recruits specific
immune cells called plasmacytoid dendritic cells which in turn drive
macrophages to an activated stage and lead to inflammation. Apart from a
potential drug target, chemerin could also be used as a biomarker to
pinpoint obese individuals who are more prone to diabetes which needs
further research [14-16].
Ectopic fat deposition, particularly in the liver and
skeletal muscle leading to dysmetabolic sequelae along with
mitochondrial dysfunction evident by decreased mitochondrial mass and/or
function are other mechanisms linking obesity & diabetes. Factors
predisposing to β-cell decompensation could also be primarily genetic or
epigenetic. Genetic studies have helped identify the role of some key
molecules in β-cell biology that may be having diabetogenic effects.
Genome- wide association scans (International Diabetes Federation) and
candidate gene approaches now have identified over 40 genes associated
with type 2 diabetes & obesity. Most type 2 diabetes genes appear to
be related to β-cell dysfunction, insulin resistance and energy
homeostssis [17,18].
Some of the glucose lowering medications are
associated with weight gain, posing a challenge to physicians &
dialectologists. Body weight with current therapeutic options needs more
consideration. With the exception of metformin, many anti-diabetes
medications are associated with weight gain like thiazolidinediones,
sulfonylureas, meglitinides & insulin. Metformin appears to have an
insulin-sparing effect and reduces weight gain with insulin treatment.
Patients with T2DM should remain on metformin when they convert to
treatment with insulin. This should be routine practice unless there is a
history of metformin intolerance or evidence of renal impairment.
Maximum weight before diagnosis of diabetes is an important predictor of
weight gain in patients taking insulin and that assessment of this
should be part of routine care [19].
The vicious cycle of increasing weight leads to
increased insulin resistance leading to increased dose of medication
& increased weight continues. This issue is particularly pressing
given accumulating evidence that even modest weight reduction- whether
through lifestyle interventions, obesity medications, or bariatric
surgery can improve glycemic control and reduce diabetes risk. It has
been shown that there is 50% reduction in prevalence of type 2 diabetes
with 5-10% weight loss in DPP study which was published in N Engl J Med [12].
The Finish Diabetes prevention study also showed similar results to DPP
study. It also showed 5% weight reduction reduces relative risk with
61% and every 3 kilos reduction in weight double this effect. Prevention
or delay of type 2 diabetes can be achieved through the adoption and
maintenance of healthy lifestyle behaviors, like those described in the
National Diabetes Prevention Program. Similarly, findings from the
Action for Health in Diabetes (Look AHEAD) trial demonstrated that
weight loss and physical activity corresponded to a marked decline in
A1C and improvements in cardiovascular disease (CVD) risk. The dramatic
increase in incidence and prevalence of obesity over the past 50 years,
associated in part with major worldwide changes in caloric intake and
dietary composition, has focused attention on lifestyle intervention to
reverse or ameliorate caloric imbalance. Successful lifestyle
intervention programs typically involve selfmonitoring of weight,
dietary intake and activity factors [20].
Medications have been used to assist in weight loss
for almost 80 years but adverse effects frequently restrict utility.
Medications have been developed based on physiological insights, more
recently targeting central nervous system control of appetite and
metabolism. However there is a growing concern regarding adverse
effects, including cardiovascular disease risk and central effects like
depression in drugs crossing the blood- brain barrier which limit
approval and application. Anti-obesity agents like
Fenfluramine/Dexfenfluramine were taken off from the market in 1997,
Ephedra in 2004, Rimonabant in 2006 & Sibutramine in 2010 due to
several side effects.
Health benefits of bariatric surgery include
substantial and sustained weight loss, resolution of comorbidities such
as diabetes, hypertension and dyslipidaemia and reduced myocardial
infarction. There is also a growing movement toward using surgery to
control diabetes but there are currently few scientifically valid data
to support this .Bariatric surgery falls into two general categories:
purely restrictive procedures such as the laparoscopic adjustable
gastric band devices, which appear to improve diabetes via weight loss,
and procedures bypassing the proximal gut, such as the Roux-en-Y gastric
bypass (RYGB) or newer gastric sleeve procedures. The latter approaches
(metabolic surgery) appear to produce unique effects on enteroendocrine
hormones and neuronal signaling pathways and produce more weight loss
and diabetes remission than banding alone [21].
The pharmacological & surgical treatment is not
feasible always .Thus, the search must continue for how to implement
optimal lifestyle interventions and to find effective drugs and/ or
minimally invasive devices. The optimal lifestyle modification which
include an individualized structured diet plan & exercise programme
is not feasible always in most situations because of the current work
culture all over the world. To address this problem the American
Diabetes Association issued new recommendations on physical activity and
exercise for People with Diabetes in November 2016. The most notable
recommendation calls for three or more minutes of light activity, such
as walking, leg extensions or overhead arm stretches, every 30 minutes
during prolonged sedentary activities for improved blood sugar
management, particularly for people with Type 2 diabetes & obesity.
This is a shift from the Association's previous recommendation of
physical movement every 90 minutes of sedentary time.
These barriers to effective management is complicated
in the context of type 2 diabetes. Obese patients with hyperglycemia
are often poorly characterized not only in terms of their history of
obesity but also in the duration of their glucose intolerance. Further,
interventions are typically started late in the disease. Although
controlling body weight (either by reduction or by prevention of further
rise) improves glycemic control by ameliorating both insulin resistance
and β-cell dysfunction, the impact of pharmacologically induced
improved glycemic control on body weight varies by individual drug. A
better understanding of mechanisms linking obesity, insulin resistance
and type 2 diabetes may ultimately facilitate more individualized
treatment. Innovative approaches to managing obesity may lower certain
barriers undermining treatment of both obesity and type 2 diabetes [22-24].
For example, modulating the incretin axis may benefit
both energy balance and glycemia. Novel pharmacological development may
depend on information gained from more efficient use of genomic,
proteomic, and metabolomic approaches and from information learned from
studying weight- loss mechanisms in bariatric surgery. In addition,
co-opting less traditional organs such as the brain and gut into the
core pathophysiology of type 2 diabetes may reveal new biomarkers which
will help in targeting therapeutic intervention. Finally, safe and
effective centrally acting drugs that decrease appetite or increase
satiety are urgently needed.
Conclusion
It is most important to emphasize primary prevention
of obesity and type 2 diabetes rather than focusing on secondary and
tertiary intervention. Physicians often introduce secondary
interventions when patients surpass the BMI threshold or when patients
self-identify, for cosmetic or health reasons. They introduce tertiary
intervention when obesity-related complications develop such as
diabetes, hypertension, or sleep apnoea. Emphasizing obesity prevention
is urgent and must include cooperation of public & private health
care system including the food industry sector. Some countries had
already taxing for high fat diet.
The insights that improve obesity prevention and
treatment will almost certainly benefit the incidence and care of type 2
diabetes. The converse may not be true since current treatments of
diabetes can have differential effects on weight. Even so, we have
reached a point when we can begin to consider innovative and potentially
more effective approaches to managing both obesity and type 2 diabetes
by using either weight loss or weight neutral diabetic regimens.
Holistic and collaborative approach is the key to success in a diabesity
clinic where the team includes dialectologist, well trained nurse,
dietitia, physiotherapist psychologists & bariatric surgeon. As per
the American diabetes association guidelines one must reduce the
sedentary time. Cutting upon sitting time, improving on standing time
& short movement activity in a periodic interval along with proper
meal plan will definitely help us to achieve freedom from obesity &
diabetes. Let us join hands to fight & make the world free from this
pandemic.
To Know More About Current Research in Diabetes & Obesity
Journal Please click on:
https://juniperpublishers.com/crdoj/index.php
https://juniperpublishers.com/crdoj/index.php
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