Exploring the Interplay: A Systematic Review of Obesity and Diabetes

This assignment is a literature review investigating the link between obesity and diabetes. It uses a systematic approach to analyze fifteen articles published within the last five years, focusing on the impact of obesity on insulin resistance and beta cell dysfunction. The review covers theoretical models such as the accelerator hypothesis, the role of excessive free fatty acids and ectopic fat storage, the influence of gut microbiota, and the impact of severe inflammation and immune system activation. The findings highlight obesity as a significant risk factor for both type 1 and type 2 diabetes, identifying specific mechanisms through which obesity influences these conditions. The study concludes that obesity substantially increases the risk of diabetes manifestation.

Running head: Obesity and Diabetes 1
The Link Between Obesity and Diabetes
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Running head: Obesity and Diabetes 2
Table of Contents
ABSTRACT...............................................................................................................................3
CHATPER ONE: INTRODUCTION........................................................................................4
1.1 Background Information..................................................................................................4
1.2 Descriptive Epidemiology................................................................................................5
CHAPTER TWO: METHODS USED TO CONDUCT A SYSTEMATIC LITERATURE
REVIEW....................................................................................................................................6
2.1 Inclusion and Exclusion Criteria......................................................................................6
2.2 Key Search Terms............................................................................................................6
CHAPTER THREE: RESULTS OF THE SYSTEMATIC LITERATURE REVIEW.............7
3.1 Theoretical Models...........................................................................................................7
3.1.1 Accelerator Hypothesis..............................................................................................7
3.1.2 Excessive FFAs and Ectopic Fat-Storage Syndrome................................................7
3.1.3 Gut Microbiota and the Development of Obesity and Type 2 Diabetes....................8
3.1.4 Severe Inflammation and the Activation of the Immune System..............................9
3.1.5 Occupational Risk and Lifestyle Factors...................................................................9
3.2 Methodologies Used.......................................................................................................10
3.3 Synthesis of Research Findings......................................................................................11
CHAPTER FOUR: DISCUSSION..........................................................................................16
4.1 Brief Summary of Main Findings...................................................................................16
4.2 Strengths and Limitations of Systematic Literature Review..........................................17
4.2.1 Limitations...............................................................................................................17
4.2.2 Strengths..................................................................................................................17
4.2.3 Policy Implications..................................................................................................17
4.2.4 Key Stakeholders.....................................................................................................18
4.2.5 Recommendations for Future Research...................................................................18
CONCLUSION........................................................................................................................19
References................................................................................................................................20
Appendix: Matrix Table for Literature Review.......................................................................26

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ABSTRACT
Background: The increase in the prevalence of obesity and diabetes in both adults and
children is alarming. Studies attribute this prevalence to behavioural changes. However, there
is need for more information on the association between obesity and diabetes in order to
provide effective interventions that are based on cause to effect. This review aims at
investigating the link between obesity and diabetes.
Methods: A systematic literature review on the link between obesity and diabetes was carried
out. A total of fifteen articles published within five years were included in the assessment.
Seven of the reviewed articles were primary articles while the other eight were literature
reviews.
Results: There is a strong association between obesity and diabetes. This can be attributed to
the effect of body weight on insulin resistance and beta cell dysfunction. Insulin sensitivity is
affected bay lifestyle behaviours such as physical activity and sleep, but obesity is the leading
factor that influences the manifestation of metabolic diseases. Both T2D and obesity are
characteristic of elevated production levels of NEFAs which is also linked to insulin
resistance in both cases. Fat distribution, dysfunction of beta cells, BMI at any level of weight
gain, Excessive FFAs and ectopic fat storage, and Gut microbiota are all linked to insulin
resistance and ultimately to the development of diabetes.
Conclusion: Obesity is the most substantial risk factor for the manifestation of diabetes. The
current study identified the mechanisms in which obesity influences both type 1 and type 2
diabetes.

Running head: Obesity and Diabetes 4
CHATPER ONE: INTRODUCTION
1.1 Background Information
Diabetes mellitus (DM) is a chronic disease that is capable of changing the metabolism of
protein, carbohydrate and fat. The disorder is a result of the unavailability of insulin secretion
caused by the inability of the beta Langerhans islet cells found in the pancreas to secrete
insulin, or it’s caused by the complications in the uptake of insulin in the proximal body
tissues. DM is further categorised into two groups namely type 1 and type 2 diabetes (Kahn,
Cooper, & Del Prato, 2014). Type 1 diabetes (T1D) is most prevalent in children, however it
can sometimes occur in adults, especially those age thirty years and above. It is commonly
the case that type 1 diabetic patients are not obese but are often diagnosed with diabetes
ketoacidosis which is an emergency status (American Diabetes Association, 2014).
The pathophysiology of type 1 diabetes shows that it is an autoimmunity (Stankov, Benc, &
Draskovic, 2013). The prevalence of type 1 diabetes is highest in the presence of other
autoimmune diseases such as Addison’s disease. The pathophysiology and aetiology of type
2 diabetes (T2D) is rather different from type 1 diabetes. The prevalence of type 2 diabetes
increases with the increasing presence of diabetes among other factors associated with it such
as physical inactivity, unhealthy diet, and urbanization (Tai, Wong, & Wen, 2015).
The increasing cases of obesity in both adults and children have been associated with the
corresponding rise in the incidence of type 2 diabetes (Bhupathiraju, & Hu, 2016). On the
other hand, the specific mechanism which leads to the increased prevalence of type 1 diabetes
is still under investigation. However, studies have shown that it is as a result of both
environmental and genetic factors (Atkinson, Eisenbarth, & Michels, 2014). Other studies
have also found out that there is a relationship between type 1 diabetes and weight gain
(Baidal et al., 2016). There is a strong relationship between obesity and type 2 diabetes which
are both related with insulin resistance. Type 2 diabetes is characteristic of endothelial

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dysfunction which has also been associated with insulin resistance or obesity. Weight gain
and insulin resistance causes type 2 diabetes due to the inability of beta cells to fully
compensate for the poor insulin sensitivity (Ye, 2013).
1.2 Descriptive Epidemiology
Diabetes and obesity have not only reached epidemic levels but have become public health
issues in the United States and worldwide. Global statistics indicate that obesity is a much
bigger problem than hunger, and the major cause of morbidity and death across the globe
with this state of conditions expected to increase in the future. Almost one out of 10 adults in
the US have diabetes with 90% of these being diagnosed with type 2 diabetes. It has
historically been assumed that diabetes is an adult disorder, but the recent rise in body weight
in children and young adults have led to the rise in the type 2 diabetes cases, more so among
the Hispanic young adults (46.1%) and Blacks (57.8%) (Menke, Casagrande, Geiss, &
Cowie, 2015). The management and treatment of obesity and diabetes is too costly
(American Diabetes Association, 2013). The healthcare expenses for obese patients is higher
by 42% compared to those of normal-weight, whereas it is double the rate for diabetic
patients compared to non-diabetic individuals (Mozaffarian et al., 2015). Both diabetes and
obesity are correlated, intricate disorders which can significantly be prevented and treated
(Ley, Hamdy, Mohan, & Hu, 2014). Both diseases increases the risk for cardiovascular
illnesses and cerebrovascular accident. Owing to the cost and increasing incidences of both
diabetes and obesity cases across the globe, it is important that critical analysis is done on the
studies that explore the association between the two conditions. This paper provides a critical
review of modern literature on the links between obesity and diabetes.

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CHAPTER TWO: METHODS USED TO CONDUCT A SYSTEMATIC
LITERATURE REVIEW
2.1 Inclusion and Exclusion Criteria
The researcher critically investigated appropriate articles and books relevant to the study
topic. Search engines like Google Scholar, PubMed, PMC, and BMC to carry out a
systematic research to find out the studies that focused on diabetes and obesity. The search
was only restricted to articles published within five years. The articles had to be on the link
between diabetes and obesity. 80 studies were retrieved from the databases after
identification, screening, and quality check. 50 articles were then included for assessment. 10
articles were not included due to duplication. Out of the 40 remaining articles, fifteen of them
were being sold and thus did not have open access. Further suitability assessment led to the
exclusion of ten more studies leaving the researcher with fifteen articles that fully met the
inclusion criteria. Among the fifteen articles, eight of them were literature reviews and the
other seven were primary articles. As a result of the critical review, different themes were
ascertained such as theoretical models, research methodologies, and the synthesis of the
findings as shown in the literature section of this paper.
2.2 Key Search Terms
The key search terms used during the research include obesity, diabetes mellitus, type 1
diabetes, type 2 diabetes, diabetes management, diabetes prevention, insulin resistance, and
prevalence.

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CHAPTER THREE: RESULTS OF THE SYSTEMATIC LITERATURE REVIEW
3.1 Theoretical Models
The researcher ascertained several theories which explain the relationship between diabetes
and obesity or weight gain.
3.1.1 Accelerator Hypothesis
The study by Al-Goblan, Al-Alfi, and Khan (2014) examined the accelerator hypothesis and
found a significant association between diabetes and obesity. The authors ascertained that the
risk of developing type 1 diabetes was significantly associated with weight gain among
youths. This is because the increase in body weight fosters insulin resistance, thus causing the
development of type 1 diabetes in people who are genetically predisposed to diabetes.
Similarly, type 2 diabetes and obesity are linked to insulin resistance because of the inability
of the beta cells to fully compensate for the low insulin sensitivity. Obesity or insulin
resistance in pre-diabetes or diabetic conditions are influenced by the endothelial dysfunction.
3.1.2 Excessive FFAs and Ectopic Fat-Storage Syndrome
Saboor Aftab, Reddy, Smith, and Barber (2014) theorised that overall and abdominal
adiposity is closely related to the development of T2D, pointing out to the significance of
waist diameter in clinical evaluation (Scott et al., 2014). Factors such as abdominal obesity,
BMI measurement, and sagittal abdominal diameter are implications for the primary role of
central adiposity in the development of T2D (Pajunen et al., 2013). High levels of visceral fat
leads to excessive production of free fatty acids (FFAs) which end up reaching the liver
through the portal vein causing fatty liver. This condition is linked to increased levels of non-
esterified fatty acid (NEFA) in the plasma which consequently leads to insulin resistance
through the Randle’s effect in the proximal body tissues such as muscles which are also the
targets of insulin (Byrne, & Targher, 2014; Ye, 2013). In the hypothesis of ectopic fat
storage, there seems to exist a depot limit for the visceral tissue, outside which the expanding
depot of the adipose tissue cannot properly store the increased fat (Choe, Huh, Hwang, Kim,

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& Kim, 2016; Boren, Taskinen, Olofsson, & Levin, 2013). As a result, the excess fat is
deposited in the sites of extra adipose tissue such as skeletal muscles, liver among others,
leading to elevated levels of insulin resistance, damaged function of the beta cells and finally
T2D (Lafontan, 2014; Rutkowski, Stern, & Scherer, 2015). Vasques et al. (2015) also found
out that sagittal abdominal circumference could be used as a predictor of insulin resistance
among people of different ethnicities.
The adipocytokines are also believed to be instrumental in the development of T2D that is
associated with obesity. The obese adults undergo expansion of fat mass which causes the
adipocytes to secret fatty acids, different adipocytokines and inflammation of mediators
(McGown, Birerdinc, & Younossi, 2014; Blüher,2014). The adipose tissue then responds to
the varying nutrient and neuro-hormonal indicators by producing adipocytokines that regulate
eating, immunity, and thermogenesis. Consequently, the sensitivity of insulin towards the
various organs of target are altered by the adipocytokines, and thus leading to obesity which
is associated with T2D (Nakamura, Fuster, & Walsh, 2014; Smitka, & Marešová, 2015).
3.1.3 Gut Microbiota and the Development of Obesity and Type 2 Diabetes
There is evidence of a strong relationship between gut microbiota and the development of
obesity by influencing different factors such as increasing food intake, intestinal
permeability, and inflammation among others (Devaraj, Hemarajata, & Versalovic, 2013;
Naseer et al., 2014). This theory is based on the findings that some types of bacteria
belonging to the gut microbiota are actively responsible for the uptake of nutrients and
dispensing energy. Whereas the lipopolysaccharide (LPS) which is secreted in the gut which
is home to several microbes may be an inducing element and linking inflammation to the
unhealthy diet characteristic of excess fats which causes obesity (Devaraj, Hemarajata, &
Versalovic, 2013). The gut microorganisms increase the absorption of monosaccharide from

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the intestinal tract and trigger the host to increase the hepatic secretion of triglycerides. This
activity fosters elevated levels of insulin resistance (Mikkelsen et al., 2015).
3.1.4 Severe Inflammation and the Activation of the Immune System
Esser, Legrand-Poels, Piette, Scheen, and Paquot (2014) theorised that severe inflammation
and the activation of the immune system triggers insulin resistance which is associated to
both T2D and obesity. The common sites of inflammation in obese cases include the muscles,
liver, and adipose tissue. The permeation of some immune cells and macrophages takes place
in these organs causing a shift in cell population which enhances inflammation. These cells
are vital in the secretion of cytokines which encourage inflammation and thus altering the
signalling of insulin in the proximal tissues or trigger the dysfunction of beta cells leading to
inadequate insulin.
Obesity which leads to type 1 diabetes is as a result of lack of physical activity. Being
physically active increases fitness in people with T1D, however the decreased fitness level in
youths is an indication of low aerobic power and strength. The routine involvement in
physical activities is enhances lipid levels, insulin resistance, and endothelial function, with
the exception of blood pressure in people with type 1 diabetes (Minges, Whittemore, & Grey,
2013; Liese, Ma, Maahs, & Trilk, 2013).
3.1.5 Occupational Risk and Lifestyle Factors
Poulsen, Cleal, Clausen, and Andersen (2014) found out that both occupational risk and
lifestyle factors were influential in developing diabetes. BMI above the normal body weight
is the most significant risk factor. Furthermore, overweight is related with physical inactivity,
shift work, and issues to do with sleep and health. According to Ganz, Wintfeld, Li, Alas,
Langer and Hammer (2014) there is a strong independent association between BMI and the
risk of developing T2D. The higher the BMI the higher the chances of being diagnosed with
T2D. Metabolic syndrome is high among employees due to their nature of lifestyle which is

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sedentary. This can be attributed to the socioeconomic changes and transitions in diet among
employees. Overweight is the leading metabolic syndrome among employees of North East
China in both genders (Wang et al., 2015). Pulgaron and Delamater (2014) studied obesity
and diabetes in children and demonstrates that factors such as individual history of obesity,
culture, environment and genetic are attributed to obesity risk. Costa et al. (2016) also found
out that the prevalence of obese cases in T1D children was highly associated with lifestyle
behavioural factors such as consumption of unhealthy foods, low socioeconomic activities,
and overfeeding from parents due to fear of hypoglycaemia. Bhupathiraju and Hu (2016)
opined that abdominal obesity, changes in agricultural policies, trends in physical activity and
napping, dietary changes, and genetics are the factors that foster obesity and diabetes.
3.2 Methodologies Used
Al-Goblan et al. (2014) conducted a literature review on the association between obesity and
insulin resistance (diabetes mellitus). A review was similarly conducted by Saboor Aftab et
al. (2014) on the complex relation between obesity and type 2 diabetes. Reviews on the
function of the Gut microbiota in diabetes and obesity were conducted by Naseer et al. (2014)
and Devaraj et al. (2013). Another literature review was conducted on the association
between inflammation and obesity, T2D, and metabolic syndrome by Esser et al. (2013).
Minges et al. (2013) used a systematic literature review to assess the link between physical
activity, nutrition, sleep, and sedentary lifestyle and obesity in young adults diagnosed with
type 1 diabetes. A literature review was also conducted by Pulgaron and Delamater (2014) on
obesity and T2D in children.
Vasques et al. (2015) used a multicentre population survey to ascertain whether sagittal
abdominal diameter could be used as a predictor of insulin resistance. Poulsen et al. (2014)
conducted a prospective cohort study using questionnaire to explore the relationship between
job, obesity and diabetes. A case control study was used by Ganz et al. (2014) to ascertain the

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link between body mass index and the risk of being diagnosed with T2D. Wang et al. (2015)
carried out a health screening of employees in North East China to approximate the metabolic
syndrome (overweight, T2D) prevalence among them. An analytical cross-sectional study
was conducted on type 1 diabetes to determine the frequency of obese cases in children
diagnosed with T1D and the associated factors (Costa et al., 2016). A cohort follow-up study
was conducted on healthy young adults to ascertain the incidence of diabetes overtime (Twig
et al., 2014). Lukács, Kiss-Tóth, Csordás, Sasvári, and Barkai (2018) conducted a population
based quantitative study to assess the associated risks of T2D in adolescent students
diagnosed with overweight and obesity.
3.3 Synthesis of Research Findings
A literature review on the association between obesity and insulin resistance was conducted
by Al-Goblan et al. (2014). The authors found out that there was a significant association
between BMI and diabetes and insulin resistance. The findings indicate that there is an
increase in the quantities of glycerol hormones, NEFA, among other substances that are
active in the development of insulin resistance in obese people. Furthermore, the impairment
of the function of beta cells alongside insulin resistance causes diabetes development.
Excessive weight at an early age is related to development of T1D. The authors also found
out that NEFA was key in the initiation of insulin resistance and in the compromise of the
functionality of beta cell.
Saboor Aftab et al. (2014) carried out a literature review on obesity and T2D and found out
that diabesity is as a result of the continued and excessive intake of energy-dense foods and
physical inactivity. Excessive intake of energy-dense foods caused increased fat deposition
and fosters insulin resistance. A fatty liver is caused by the release of free fatty acids (FFA) to
the liver through the portal vein. The spill of FFA into the systemic circulation leads to
liptoxicity of body tissues such as the heart and muscles causing a viscid cycle of fat damage

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and inflammation which worsens insulin resistance, dysfunction of beta cells and finally the
development of type 2 diabetes. Furthermore, the authors ascertained that an independent
determinant of insulin resistance is visceral fat content whereas adipokines prevent the
development of type 2 diabetes which is caused by obesity.
Naseer et al. (2014) conducted a literature review and examined the function of gut
microbiota in T2D, obesity and Alzheimer’s disease and showed that there was a relationship
between the human microbial flora and the manifestation of metabolic syndrome such as
T2D, obesity and other related illnesses. The gut microbiota regulates energy balance and
adiposity in the host through different process such as the rise in the uptake of energy from
nutrition, regulation of the composition of tissiue fatty acid, the modulation of peptides
secreted in the gut and bile acids. The microbiota gut is also influential in the metabolism of
sugar and lipid and in the LPS development which both fosters low grade inflammation in
obesity and type 2 diabetes which is obesity-based. Similar studies were conducted by
Deveraj et al. (2013) and found out that the gut microbes had a substantial positive effect on
the metabolic syndrome, diabetes and obesity. Elevated levels of FFA and hyperglycemia are
the typical features of obesity, diabetes, and metabolic syndrome, alongside a diet with excess
fat and energy dense foods. All these increasingly activates the inflamasome complex in
addition to increasing the activation of macrophages. Moreover, macrophages can penetrate
the adipose tissue and trigger mitogen-triggered protein kinases leading to elevated cross-talk
and adipokines. A diet rich in fat and hyperlgycemic one causes alterations in the gut
microbiome by changing the content of histidine among others causing dysfunction of the gut
and conditions common in diabetes, obesity and metabolic syndrome by altering the response
of the host.