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DSX 607 No. of Pages 7

Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxxxxx

Contents lists available at ScienceDirect

Diabetes & Metabolic Syndrome: Clinical Research &

Reviews
journal homepage: www.elsevier.com/locate/dsx

Review

Obesity and diabetes: An update

Shalini Vermaa,* , M. Ejaz Hussainb
a
b

Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia (Central University), New Delhi 110025, India
Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia (Central University), New Delhi 110025, India

A R T I C L E I N F O

Article history:
Available online xxx

Keywords:
Sleep disturbances
Perfusion
Inammation
Hormonal dysfunction
Metabolic defects

A B S T R A C T

The twin epidemic of obesity and diabetes is a major crisis globally. Several epidemiologic studies reveal
the parallel escalation of obesity and diabetes. The term diabesity expresses their close relationship to
each other, wherein both these metabolic disorders are characterized by defects of insulin action. The
pathophysiology connecting obesity and diabetes is chiey attributed to two factors: insulin resistance
and insulin deciency. Recent years have seen an increasing body of work on the following metabolic
defects common to both obesity and diabetes such as, impaired tissue perfusion, sleep disturbances,
androgen dysfunction, altered Vitamin D levels and GI stress. The scope of this review is to present the
most widely accepted theories that link the two diseases, provide an update on some proposed unifying
metabolic defects and highlight current and future prevention and management strategies.
2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Contents
1.

2.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
Obesity to Diabetes . . . . . . . . . . . . . . . .
1.1.
Allied anomalies . . . . . . . . . . . . . . . . . .
1.2.
Tissue perfusion . . . . . . . . . . .
1.2.1.
Sleep . . . . . . . . . . . . . . . . . . . .
1.2.2.
Androgens . . . . . . . . . . . . . . . .
1.2.3.
Vitamin D . . . . . . . . . . . . . . . .
1.2.4.
Gut hormones and microbiota
1.2.5.
Prevention and Therapy . . . . . . . . . . . .
1.3.
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction
The twin epidemic of obesity and diabetes is a major crisis
globally. Several epidemiologic studies reveal the parallel escalation of obesity and diabetes. The term diabesity expresses their
close relationship to each other, wherein both these metabolic
disorders are characterized by defects of insulin action [1].
Diabetes is a global health care problem that threatens to reach
pandemic levels by 2030. As of 2014, there are 387 million people
living with diabetes, worldwide. Moreover, around 316 million

* Corresponding author.
E-mail address: shaliniverma3001@gmail.com (S. Verma).

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with impaired glucose tolerance are at high risk from the disease, a
number that is set to reach 471 million by 2035. Without concerted
action to prevent diabetes, it is projected that around 592 million
people will be living with the disease in another 25 years time [2].
Further, Type 2 diabetes mellitus (T2DM) represents approximately 90% of all cases of diabetes, and its frequency is similar to that of
obesity [3].
Recent estimates indicate that obesity currently affects more
than 600 million people worldwide and is associated with more
than 45 comorbidities, in addition to several atherogenic disorders
that compose the metabolic syndrome [1]. On account of
established health risks and substantial increase in prevalence,
obesity has become a serious global health problem. The burden of
obesity is particularly high in the middle-income countries of

http://dx.doi.org/10.1016/j.dsx.2016.06.017
1871-4021/ 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: S. Verma, M.E. Hussain, Obesity and diabetes: An update, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.
org/10.1016/j.dsx.2016.06.017

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S. Verma, M.E. Hussain / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxxxxx

Eastern Europe, Latin America and Asia where it is the fth most
common cause of disease burden, ranking just below underweight
[4]. Developing countries have shown a steep rise in obesity rates
over the last two decades, owing to adoption of a Western lifestyle,
which has resulted in profound changes in the quality, quantity and
sources of food consumed, compounded by the effects of decreased
physical activity. While increase in obesity in developed countries,
which began in the 1980s and accelerated from 1992 to 2002, has
slowed since 2006, the increase is likely to continue in developing
countries, where almost two-thirds of the worlds obese population currently resides [5].
The scope of this review is to present the most widely accepted
theories that link the two diseases, provide an update on some
proposed unifying metabolic defects and highlight current and
future prevention and management strategies.
1.1. Obesity to Diabetes
The increase in the prevalence of type 2 diabetes is closely
linked to the upsurge in obesity. It is estimated that about 90% of
T2DM is attributable to excess weight [4]. The pathophysiology
connecting obesity and diabetes is chiey attributed to two factors:
insulin resistance and insulin deciency [6] (Fig. 1). Obesity causes
sustained elevation in plasma FFA levels, both in the basal state and
following glucose load which present a major factor for insulin
resistance [7,8]. Source of the FFA excess in obese individuals are
considered the meal-derived fatty acids and lipolysis of the adipose
tissue [1]. Furthermore, central-abdominal fat is metabolically and
lipolytically more active, releasing more FFAs in the bloodstream
[9]. Clinical studies in healthy volunteers with acute elevation of
plasma FFAs resulted in whole body insulin resistance [10].
Increased plasma FFAs by mass action augment their cellular
uptake and induce their mitochondrial b-oxidation, blocking at the
level of substrate competition, intermediates accumulation,
enzyme regulation, intracellular signaling and/or gene

transcription the glucose metabolism [1]. The predominant

utilization of lipids at the expense of glucose, shown by the
increase in lipid oxidation induces a diminution of glucose uptake
by muscle and decreased rates of glycogen synthesis in skeletal
muscle [1113]. This state of chronic hyperglycemia (glucotoxicity)
further impairs insulin sensitivity. Hyperglycemia and compensatory hyperinsulinemia associated with insulin resistance and
glucose intolerance lead to pathological glycation of circulating
proteins and formation of advanced glycation end products. This
progression ultimately leads to a pancreatic beta cell secretory
failure and apoptosis.
Ravussin et al. [14] showed that when the diet-derived fat
intake is increased, fat storage within and around other tissues and
organs including liver, skeletal muscle and pancreatic b-cells,
which under normal conditions do not store lipids, takes place.
This in turn results in excessive mitochondrial production of toxic
reactive lipid species that cause organ-specic oxidative damage
and cellular dysfunction, leading progressively to the development
of insulin resistance, impaired glucose metabolism and nally to
diabetes [15]. The accumulation of toxic metabolites within the
pancreatic islet b-cells in particular affects insulin secretion and
enhances b-cell apoptosis accelerating the progression to overt
diabetes [1]. At the cellular level, the progression from insulin
resistance to diabetes is accompanied by oxidative stress and
systemic inammation. Increasing evidence suggests that chronic
low-grade inammation in adipose tissue affects the pathogenesis
of diabetes in obese patients [16]. (Table 1 enumerates major
biomarkers contributing to inammation in obesity and diabetes).
Obesity induces inammation via LPS-related endotoxemia
involving gut microbiota [3]. Inammation is characterized by
an upsurge of T-lymphocytes and M1 macrophages which have
increased secretion of proinammatory cytokines that act to
perpetuate systemic inammation and induce insulin resistance
[3]. In addition, inammatory signals associated with obesity
compromise endoplasmic reticulum function and result in marked

Obesity

Permanent elevaon of FFA

Accumulaon of TG in liver and beta cells

Inhibit glucose transport acvity

Predominant ulizaon of lipids by muscle

Glucose uptake by muscle

Chronic hyperglycemia

Glycogen synthesis in skeletal muscle

(Glucotoxicity)

INSULIN RESISTANCE

Hepac and islet dysfuncon

(Sustained Hyperinsulinemia)

(Lipotoxicity)

Impairs insulin sensivity

Oxidave stress and Systemic inammaon

INSULIN DEFICIENCY

DIABETES
Fig. 1. Pathways from obesity to diabetes.

Please cite this article in press as: S. Verma, M.E. Hussain, Obesity and diabetes: An update, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.
org/10.1016/j.dsx.2016.06.017

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S. Verma, M.E. Hussain / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxxxxx

Table 1
Major biomarkers contributing to inammation in obesity and diabetes.
Inammatory mediators in obesity and diabetes
Immune cells

Role

Obesity and Diabetes

M1: proinammatory; M2: anti-inammatory

ATMs
Dendritic cells Involved in macrophage (M1) activation and accumulation at inammation site
Eosinophils
ILC2

Improve glucose homeostatsis by sustaining levels of M2 macrophages (through IL-4 and IL-13
signaling)
Promote accumulation of eosinophils and M2 macrophages (through IL-5 and IL-13)

CD4 cells
CD4+ FOXP3+
CD8+

Th1 and Th17: proinammatory; Th2: anti-inammatory

Immunosuppressive role
Secretion of proinammatory cytokines and cytolysis

NK cells

Secrete proinammatory cytokines

B-cells
Mast cells

Promote IR by inducing M1 macrophages

Involved in allergy and anaphylaxia

Switch M2 ! M1
Increased levels: obese, type2 DM
Decreased: improved IR
Reduced with increased fat mass
Decreased responses in White Adipose Tissue in
obesity
Increased Th 1/Th 2 ratio
Reduced in insulin resistance
Elevated in obese adipose tissue
Genetic depletion lowers inammation and
systemic IR
Loss of NK cells has modest effect on weight gain
and IR
Elevated in adipose tissue after high fat diet
Multifold increase in obesity

Interleukins
IL-1b

Impairs insulin signaling

Increases lipolysis
Proinammatory cytokine
Suppresses insulin action
Induces production of CRP
Anti-inammatory cytokine

IL-6

IL-10

Increased levels contribute to beta cell destruction and loss causing insulin resistance and diabetes
Positively correlated with obesity, glucose intolerance, insulin resistance

Reverses negative regulation of GLUT4 and IRS-1 stimulated by TNF restoring insulin signaling

Cytokines

Role

Obesity and Diabetes

Leptin

Control food intake and increase energy expenditure via receptors in hypothalamus
Induce expression of proinammatory cytokines contributing to adipose tissue inammation
Improves insulin sensitivity
Inhibit FFA uptake and oxidation
In adipose tissue, increases glucose uptake and adipogenesis
Proinammatory cytokine
Induces insulin resistance
Inhibits LPL activity
Increases FFA mobilization from adipose tissue
Induces macrophage iniltration, insulin resistance and TG accumulation in liver
Regulates immune responses
Involved in inammatory process associated with obesity [18]
Regulation of glucose metabolism and apoptosis of beta cells [18]

Leptin resistance and hyperleptinemia

Adiponectin

TNF

CCL2
TGF
MIF [18]

Levels decrease with adiposity

Linked to obesity and insulin resistance

Increased levels in diabetes

Positively associated with the grade of obesity
Increased serum levels

Adapted from Solange et al. [3] Low-Grade Inammation, Obesity, and Diabetes.

JNK activation in insulin-sensitive tissues, such as fat and liver.

Activated JNK, specically the JNK1 isoform, play a dominant role
in insulin receptor substrate-1 serine phosphorylation and
subsequent inhibition of insulin action [17].
1.2. Allied anomalies
Recent years have seen an increasing body of work on the
following metabolic defects common to both obesity and diabetes:

Impaired tissue perfusion

Sleep disturbances
Androgen dysfunction
Altered Vitamin D levels
Gastrointestinal stress

1.2.1. Tissue perfusion

A vicious circle of progressive microvascular dysfunction both
contributes to and is exacerbated by worsening insulin resistance.
Capillary recruitment is an important mechanism by which insulin
promotes uptake of glucose from the blood [19]. Impaired
recruitment and rarefaction may, therefore, reduce glucose uptake
and contribute to insulin resistance [20]. There is considerable
evidence to suggest that insulin resistance and hyperglycemia,

acting via oxidative stress, inammation, and advanced glycation

end products, can induce microvascular abnormality [21] causing
increased microvascular permeability in diabetes [22]. Several
studies have shown impaired coronary ow reserve in diabetic
individuals in the absence of coronary artery stenosis [2326]. An
inverse relation between hyperemic myocardial blood ow and
fasting insulin level has also been found among healthy, nonobese
individuals, which suggests that even mild insulin resistance is
associated with impaired coronary ow reserve [27].
Microvascular function is found to be negatively correlated with
adiposity [28]. Proposed mechanisms include:
a) Obesity associated oxidative stress and reduced nitric oxide
availability as important mechanisms in the development of
microvascular rarefaction [29].
b) Excess adiposity is associated with a chronic state of vascular
inammation, with increased levels of proinammatory
cytokines, particularly, production of tumor necrosis factor
(TNF), which is negatively correlated with skin capillary
recruitment and insulin sensitivity [30]. Deposits of fat around
arterioles may be involved in local TNF- signaling and
consequently impaired perfusion and insulin resistance [31].
c) Increased fat mass leading to prolonged elevation of free fatty
acid levels in the blood, which can impair capillary recruitment
[32].

Please cite this article in press as: S. Verma, M.E. Hussain, Obesity and diabetes: An update, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.
org/10.1016/j.dsx.2016.06.017

G Model
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1.2.2. Sleep
Epidemiological studies have established the association of
short sleep with an increased prevalence of type 2 Diabetes and
obesity [3339]. The cross-sectional observations of lower leptin
and higher ghrelin concentrations in decreased sleep duration,
independent of BMI, have led to hypothesizing that such hormonal
changes promote overeating and lead to increased risk of obesity
[40,41]. Furthermore, BMI was found to be inversely proportional
to sleep duration in persons sleeping <8 h [40].
Experimental studies have demonstrated a decrease in glucose
tolerance as a result of partial sleep deprivation [42]. Additionally,
partial sleep restriction caused a reduction in leptin, elevation in
ghrelin and an increase in hunger and appetite ratings with
preference for calorie-dense higher carbohydrate content food
when caloric intake was kept constant [43]. It also resulted in
impaired insulin signaling in abdominal fat tissue with a
concurrent decrease in whole body insulin sensitivity [44]. Sleep
restriction to 4 h compared to 8.5 h time in bed resulted in
increased endogenous glucose production, indicating hepatic
insulin resistance [45] and decreased glucose disposal rate
reecting decreased peripheral insulin sensitivity. Prolonged
partial sleep restriction could also contribute to obesity and
diabetes by the means of chronic, low-grade inammation as
shown by an increase in the level of proinammatory cytokines
and altered immune [46] and stress responses resulting from the
loss of sleep [47].
1.2.3. Androgens
There is a bidirectional modulation of glucose homeostasis by
androgens in males and females. Androgen deciency in males and
androgen excess in females produce metabolic dysfunction via
decient or excessive androgen-receptor (AR) action, respectively,
in multiple tissues including the central nervous system, liver,
skeletal muscle, adipose and b-cells [48].
Males exhibit an inverse correlation between total serum
testosterone and the amount of visceral adipose tissue [49].
Testosterone action prevents fat accumulation in males via a
combination of Estradiol-receptor and androgen-receptor mediated effects. Several studies suggest that the suppressing effect of
testosterone on white adipose tissue tissue is indirectly mediated
via AR signaling in skeletal muscle that (a) Stimulates the
commitment of pluripotent mesenchymal stem cells into myogenic lineage while at the same time suppressing the adipogenic
lineage [50] and (b) Indirectly decrease adipose tissue mass by
increasing muscle oxidative metabolism [51]. Low testosterone
levels are associated with low PGC1 expression [52], a molecular
marker of muscle insulin sensitivity that stimulates mitochondrial
biogenesis and skeletal muscle oxidative bres [51].
In women, however, hyperandrogenism predisposes to T2DM.
Higher levels of free testosterone and low concentration of sexhormone binding globulin (SHBG)-which increases free testosterone, have been repeatedly associated with glucose intolerance and
insulin resistance in women [5357]. High testosterone levels
produce insulin resistance by decreasing insulin stimulated whole
body glucose uptake in healthy pre- and postmenopausal women
[54,5860]. Moreover, this reduced insulin stimulated whole body
glucose uptake was not attributable to hepatic insulin resistance,
which remained unchanged, supporting a role for skeletal muscle
in insulin resistance [58]. Role of excess testosterone in promoting
skeletal muscle insulin resistance with ber type switch has also
been conrmed in studies [61,62]. Generally, insulin sensitivity is
shown to be improved when hyperandrogenism is reversed with
anti-androgen therapy, in association with weight loss [6365].
Androgen excess also prevents leptin from activating brown
adipose tissue thermogenesis, which is associated with reduced

energy expenditure and visceral obesity [48]. Summarily, in

women with a prior b-cell defect, excess testosterone may
increase predisposition to b- cell failure through the cumulative
action of various b-cell stresses, including insulin resistance and
circulating oxidative stress [58].
1.2.4. Vitamin D
There is evidence that vitamin D acts at multiple sites to inhibit
fat accumulation, increase insulin synthesis and preserve pancreatic islet cells, decrease insulin resistance and reduce hunger,
favoring obesity and T2DM control [66].
In adipocytes, vitamin D appears to inhibit the active form of
adipogenic transcription factors and fat accumulation during the
differentiation phase [67]. Additionally, since there are VDREs in
the insulin promoter genes [68], it is proposed that vitamin D
modulates insulin synthesis in the b-pancreatic cells, mediated by
nVDR. Vitamin D may also promote morphological improvements
in pancreatic islet cells, decrease apoptosis, and have nongenomic
effects via the mVDR [69]. In skeletal muscle, there is evidence that
vitamin D can decrease insulin resistance and increase glucose
uptake [70]. Moreover, decreased levels of serum vitamin D can
reduce circulating calcium and induce secondary hyperparathyroidism [71]. The parathormone (PTH) chronically increases
intracellular levels of ionic calcium in adipocytes, which may act
reciprocally on increased expression of fatty acid synthase (FAS)a
key regulatory enzyme in the deposition of lipidsand on
decreased lipolysis. Also, decreased thermogenesis and lipid
oxidation through the down-regulation of uncoupling proteins
have been suggested [72]. Thus, an increase in PTH may induce
weight gain, obesity, and T2DM. Other targets of vitamin D action
are immune cells where it reduces the hypersecretion of chemokines and cytokines in monocytes [73], and control functions,
maturation and/or growth of T cells [74], B cells [75] and dendritic
cells [76], to generate a more tolerant and anti-inammatory
response prole.
1.2.5. Gut hormones and microbiota
Incretins, are gut-derived hormones released predominantly by
the L cells in the distal bowel in response to a meal [77]. They work
by enhancing the insulin release from pancreatic beta cells and
inhibiting postprandial glucagon secretion and gastric emptying
after a meal [78] bringing about a reduction in blood sugar
concentrations. Ghrelin, a peptide produced by the stomach,
stimulates appetite and has a pro-diabetic role, causing hyperglycemia through inhibition of insulin resistance and stimulation of
release of counter-regulatory hormones, and impairing insulin
sensitivity [79]. Its levels increase with fasting and decrease after a
meal [80]. Another peptide Obestatin, derived from ghrelin
precursor but with opposite effects has recently been found to
be produced by the same neuroendocrine cells that secrete the
orexigenic hormone. It counterbalances the effects of ghrelin by
decreasing appetite [81].
Studies have consistently shown the association between obesity
and unbalanced dominant gut phyla, with reductions in Bacteroidetes and a proportional increase in Firmicutes [8287]. Obesity is
closely related to endotoxemia because of the increased intestinal
permeability [88]. It has been proposed that high fat diets by means
of reducing the expression of tight junction proteins and modulating
the gut microbiota, increase the intestinal permeability leading to
metabolic endotoxemia associated with increases in inammatory
tone, body weight gain, and insulin resistance [88].
1.3. Prevention and Therapy
The mainstay for the prevention, amelioration and treatment of
obesity and the associated insulin resistance constitute strategies

Please cite this article in press as: S. Verma, M.E. Hussain, Obesity and diabetes: An update, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.
org/10.1016/j.dsx.2016.06.017

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that reduce fat mass. Lifestyle modications such as controlled

caloric intake, healthy diet and increased physical activity remain
the rst line treatment, while anti-obesity drugs (orlistat, siutramine) and bariatric surgery work additionally for loss of the
excessive body weight.
The rst T2DM therapeutics to target the beta cells was the
sulfonylurea compounds, which act directly on the ATP-sensitive
potassium channels of the beta cell to enhance membrane
depolarization, stimulating exocytosis of insulin granules [89].
However, sulfonylureas act in a glucose-independent manner,
increasing the potential risk of hypoglycemia [90]. Furthermore,
sulfonylureas and other long established therapeutics, including
the insulin-sensitizer metformin, do not prevent the continuing
loss of beta cell function observed in T2DM [91]. Incretin-based
therapies are increasingly being used in clinical practice for the
management of T2DM [92,93] that address a different aspect of
beta cell dysfunction: the lack of potentiation of insulin secretion
in response to an oral glucose/nutrient challenge [94]. This
potentiation occurs because of incretins that act on the pancreas
and other peripheral tissues to elicit biological effects, including
augmenting nutrient-stimulated insulin secretion. This effect of
incretins is lost or blunted in T2DM [95]. Therapeutic approaches
for enhancing incretin action include degradation-resistant
Glucagon-like Peptide 1 (GLP-1) receptor agonists (incretin
mimetics) and inhibitors of Dipeptidyl Peptidase 4 (DPP-4) activity
(incretin enhancers) [92]. In addition to their incretin effect, they
exert a glucose-lowering effect with no or only a minimal risk of
hypoglycaemia [92,96]. Moreover, DPP-4 inhibitors are weightneutral, whereas GLP-1 receptor agonists reduce body weight [92].
Several novel medications that target specic molecules and
biochemical pathways implicated in the pathogenesis of insulin
resistance including glucocorticoid receptor inhibitors and factors
that reverse endoplasmic reticulum stress and restore it, promise
more effective treatment of insulin resistance in the future. Finan
[97] and colleagues have reported the discovery of a new agonist
that simultaneously targets three key metabolically related
peptide hormone receptorsthe receptors for glucagon-like
peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide
(GIP) and glucagon. This unimolecular triagonist was proved to be
remarkably effective at reducing body weight, improving glucose
control and reversing hepatic steatosis. Recent studies on the
administration of nutritional supplements (e.g. chromium, magnesium, vitamin D) and probiotics that alter gut ora to lean type
for the amelioration of insulin resistance and diabetes have gained
many supporters. Similarly do the centrally acting insulin
sensitizers including leptin and dopamine D2 receptor agonists
[1]. Their role however in clinical practice remains to be proved.
The effects of physical activity in improving metabolic prole in
obesity and diabetes have been unequivocal. Studies have
consistently shown improved glycemic control [98103], lipid
prole [100,101], cardiovascular tness [101,104106], antioxidant
status [107,108], quality of life [109111] and reduced inammatory markers [108,112116], adiposity [103,117120] and atherogenic progression [113], establishing physical activity as an
evidence-based treatment modality to combat diabesity. The joint
position statement of ACSM and ADA [121] recommends
undertaking exercise as a safe and effective measure for diabetes
management and prescribes the following dose. Aerobic training to
be performed at least 3 days/week with no more than 2
consecutive days between activity bouts, at a moderate intensity
(4060% VO2 max) for a minimum of 150 min/week. Resistance
training should be undertaken at least twice weekly on nonconsecutive days, at a moderate intensity of 50% of 1 RM involving
1015 repetitions for the major muscle groups (in the upper body,
lower body and core). The position stand of ACSM on physical
activity intervention strategies for weight management [122]

provide evidence for the prevention of weight gain, promotion of

clinically signicant weight loss and also prevention of weight
regain after weight loss with doses that approximate
250300 min/wk (approximately 2000 kcal/wk) of moderate
intensity exercise.
2. Conclusion
A signicant predisposition to insulin resistance is observed
with obesity. This review, by no means exhaustive, summarizes the
pathogenesis, mediated and inuenced by a host of common
denominators including: adipokines, immune cells, hormones,
Vitamin D, tissue perfusion and sleep. Finally, combating the twin
epidemic requires a comprehensive approach including dietary
modications and regular physical activity, augmented by newer
pharmaceutical options.
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Please cite this article in press as: S. Verma, M.E. Hussain, Obesity and diabetes: An update, Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.
org/10.1016/j.dsx.2016.06.017