The effects of diet and lifestyle

changes on insulin resistance

in type II diabetes
By Maddie Leopold, Program in Neuroscience
May 13th, 2016

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Introduction to Type II Diabetes

Type II diabetes mellitus, formerly called non-insulin-dependent diabetes mellitus or

adult-onset diabetes, is a disease of altered metabolism and nutrient storage in conjunction with

several other metabolic abnormalities such as hyperlipidemia, dyslipidemia, and hypertension

(high blood pressure), and accounts for 95% of all diabetes cases in the U.S. (Bazzano et al.,

2005). One of the most common side effects of type II diabetes is increased fat mass, which

occurs through high volumes of fatty acid release into the portal system (Han et al., 1998).

Increased fat mass and concurrently high plasma blood glucose puts individuals with type II

diabetes at increased risk of heart disease, heart attack, stroke, and Alzheimers disease, which all

have the potential to detract from an individuals quality of life and longevity (Bazzano et al.,

2005).

Type II diabetes is serious and costly a disease that effects over 29 million adults (about

10% of the population) in the United States according to the latest estimate in 2014 (Center for

Disease Control and Prevention, 2014). Another 86 million adults, which is more than one in

three individuals, have prediabetes, which is a precursor of type II diabetes 2014 (Center for

Disease Control and Prevention, 2014). Prediabetic individuals have blood sugar levels that are

higher than normal but not high enough to reach type II diabetes classification.

Diabetes rates in the U.S. have been rising steadily since the 1970s and have reached

epidemic proportions. Type II diabetes has historically been a disease that rarely affected

children (hence the former name adult-onset diabetes), but now more than 208,000 individuals

under the age of 20 have diagnosed cases of type II diabetes, and roughly 4,000 new cases in this

age demographic are diagnosed annually (Center for Disease Control and Prevention, 2014). The

costs of treating diabetes and concurrent health conditions are costing our citizens and our

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government tremendously. Total costs of diagnosed diabetes in the United states in 2014 was

$245 billion; $176 billion directly for medical costs and $69 billion in reduced productivity

(Center for Disease Control and Prevention, 2014). It is estimated that medical costs for

individuals with type II diabetes are at least twice that of most non-diabetic individuals (Center

for Disease Control and Prevention, 2014). While treatment can ameliorate some of the

complications and symptoms related to type II diabetes, it does not permanently restore healthy

plasma glucose levels or eliminate all adverse symptoms and consequences (Uusitupa et al.,

2003). Additionally, diagnosis of type II diabetes is not usually established until symptoms are

consistently present. In fact, the Center for Disease Control and Prevention (2014) estimates that

1 in 4 individuals living with type II diabetes are initially unaware of their condition. Despite

treatment efforts, the incidence of diagnosis is still rising. With this in mind, it is evident that

more focus should be placed on prevention.

Extensive research has shown that diet and lifestyle changes can have a significant

impact on reversing insulin resistance, a precursor to type II diabetes, and a more salient

treatment effect on type II diabetes than leading medications (American Diabetes Association,

2005). The implications of reversing the damage done by type II diabetes are enormous both for

the individual and for our society, which carries the burden of affording the tremendous medical

costs that are associated with this disease. This paper will focus on the genetic and environmental

risk factors that predispose individuals to type II diabetes, how insulin resistance and sensitivity

and affects metabolism, and how lifestyle changes involving diet and exercise can reverse insulin

resistance and prevent and delay the onset of type II diabetes.

Genetic and Environmental Risk Factors

Genetic Factors

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 Research suggests that type II diabetes can occur as a result of developmental

complications of the pancreas and liver. This condition is more likely to occur in individuals who

had poor fetal nutrition during critical stages of development (Han et al., 1998) (Uusitupa et al.,

2000). Individuals with hypertension, hyperlipidemia or resulting dyslipidemia are also at

increased risk for developing type II diabetes (Uusitupa et al., 2003). Additional studies have

shown that height may also play a role in diabetes risk. Han et al. (1998) found that shorter men

(in the shortest tertile for height) were five times more likely to develop type II diabetes and that

shorter women are two times more likely to develop type II diabetes. Lyssenko et al. (2008)

conducted a study that examined the interaction between environmental and genetic factors and

their influence on type II diabetes. They genotyped 16 single-nucleotide polymorphisms (SNPs)

and analyzed clinical factors in 16,061 Swedish and 2,770 Finnish participants. The incidence of

diabetes of the participants was 11.7% (2201 people) after a 23.5-year follow-up. They found

that the strongest clinical predictors of type II diabetes were a family history of the disease, high

body mass index (BMI), elevated liver-enzyme levels, smoking status, and low values of insulin

secretion and action (Lyssenko et al., 2008). They also found that variations in eleven genes were

significantly associated with the predisposition of developing type II diabetes independently of

clinical risk factors. Eight of the gene variations were linked to impaired beta-cell function

(Lyssenko et al., 2008). They concluded that in comparison with clinical risk factors, genetic

variations linked to the risk of type II diabetes had a relatively small effect on the ability to

predict the development of type II diabetes. However, the strength of genetic variation in

predicting type II diabetes increases over time (Lysskenko et al. 2008).

Environmental Factors

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 The primary environmental risk factors for developing type II diabetes are obesity,

physical inactivity, and consuming a high-fat diet that is also low in dietary fiber (Uusitupa et al.,

2003). Researchers estimate that obesity can increase the risk of developing type II diabetes

anywhere from 60% to 90%, and that there is a strong positive correlation between BMI, weight

gain, and the development of type II diabetes (Bazzano et al., 2005). New research suggests that

waist circumference to hip circumference ratio may also be one of the strongest indicators for

type II diabetes (Qiao et al., 2010). Several studies have shown that having waist circumference

that is significantly larger than hip circumference had a positive association with type II diabetes

development (Bazzano et al., 2005). The San Antonio Heart Study that examined Mexican

Americans in the U.S. aged 25-64 and in a 7-year follow-up study found that waist

circumference to hip circumference ratio was a better risk predictor for type II diabetes than BMI

(Wei et al., 1997). Snijder et al. (2003) also found that larger waist circumference is associated

with a higher risk of developing type II diabetes, but that large hip and thigh circumferences,

independent of BMI, waist circumference, and age, are not linked to a higher incidence with a

higher risk of developing type II diabetes. Taken together, this information suggests obesity and

excessive food consumption are possibly the most significant risk factors for type II diabetes.

Thus, even moderate weight loss can have major benefits on reducing type II diabetes risk in

overweight individuals.

Insulin Resistance and Sensitivity

Insulin Resistance

Insulin resistance is a condition where tissues in the body become resilient to the effects of

insulin (Kahn and Flier, 2000). When the body is in an insulin resistant state, the cells are unable

to effectively use the insulin secreted by pancreatic beta-cells, which results in high blood-sugar

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levels. Elevated blood-sugar then triggers beta-cells in the pancreas to produce even more

insulin, which causes blood-insulin levels to rise. If high blood-sugar and blood-insulin levels

become chronic, these two factors can lead to the onset of type II diabetes. Insulin resistance is

an evolved mechanism that prevents muscles from taking up the extra glucose in the blood so

that the brain has a steady supply of glucose (Bazzano et al., 2005). Kahn and Flier (2000) found

that insulin resistance in obesity and type II diabetes is often intensified by decreased insulin-

stimulated glucose transport and metabolism in adipocytes and skeletal muscle and by impaired

suppression of blood glucose. They also found that obesity is a major contributing factor to

insulin resistance. Morbidly obese participants in their study had reduced insulin signaling in

skeletal muscle which led to higher blood glucose levels (Kahn and Flier, 2000).

Factors that Increase Insulin Resistance

Diets containing high amounts of fat and sugar and low amounts of dietary fiber, such as

the typical high-fat Western diet, contribute to insulin resistance. Cordain et al. (2005) found that

long-term consumption of a high-fat and high-glycemic load diet, two primary characteristics of

the typical Western diet, can have adverse effects on metabolism and health. These health

complications include: chronic hyperglycemia and hyperinsulinemia (often indicative of type II

diabetes) which cause physiological and hormonal changes that lead to insulin resistance

(Cordain et al., 2005). Hormones such as corticosteroids, growth hormone, and nicotinic acid

have also been shown to contribute to insulin resistance. Other factors and conditions that can

increase insulin resistance include: hypertension, obesity, insufficient physical activity, age,

irregular body fat distribution, and genetics (Lindstrm et al., 2003). ADD MORE??

Factors that Decrease Insulin Resistance

Diets that contain decreased amounts of fat and increased amounts of low-glycemic,

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high-fiber carbohydrates have been show to negate the effects of insulin resistance. A low-fat,

low-sugar, and high-fiber diet can shift the body into an insulin sensitive phase and can increase

glucose tolerance (Kahn, 2003). Research indicates that regular physical activity reduces insulin

resistance, and that individuals that are in good physical shape have smaller increases of blood

insulin levels in response to glucose than do sedentary individuals. These findings suggest that

regular physical activity elevates tissue sensitivity to insulin (Bazzano et al., 2005). Hu et al.

(2001) also found that diets high in polyunsaturated fat could be beneficial for lowering insulin

resistance, and that diets high in saturated fat and trans-fat could negatively affect insulin

resistance and glucose metabolism.

ADD MORE

Insulin Sensitivity

In contrast, insulin sensitivity, which is essentially the opposite of insulin resistance, is a

state where tissues in the body are receptive to the effects of insulin and use it efficiently and

effectively. Exercise has been shown in increase insulin sensitivity. Reichkendler et al. conducted

a study in 2013 that analyzed the effects of exercise on stimulating glucose uptake in skeletal

muscle versus glucose uptake in adipose tissue and the overall effects of exercise on increasing

insulin sensitivity in insulin resistant individuals. The findings of this study are that exercising a

minimum of three to four times a week can significantly improve insulin sensitivity and glucose

uptake in skeletal muscles (Reichkendler et al., 2013). Boughouts and Keizer (2013) found in

their 2000 study that high-intensity exercise, interval training, and resistance training with

weights often maximize insulin-related benefits (Borghouts and Keizer, 2000). Goodyear and

Kahn (1998) conducted a study to build on the knowledge that exercise reduces insulin

sensitivity with a focus on changes in skeletal muscle at the cellular level. Similar to other

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research, they found that physical exercise can be greatly beneficial for both the prevention and

treatment of type II diabetes because exercise increases insulin sensitivity (Goodyear and Kahn,

1998). More specifically, they determined that even a single exercise session can significantly

increase the rate of glucose uptake and disposal and insulin sensitivity in working skeletal

muscles. These effects can last up to several hours after exercise is completed. Goodyear and

Kahn (1998) concluded that these findings and clarifications have important implications for the

efficacy of exercise in the treatment and prevention of type II diabetes because of its effect on

metabolic control and regulation of glucose homeostasis.

Effects of Lifestyle Changes on Insulin Resistance in Patients with Type II Diabetes or

Prediabetes

Overwhelming research has shown that lifestyle changes and intervention programs

associated with diet and exercise can reverse insulin resistance in diabetic individuals and also

prevent or delay the onset of type II diabetes even in high-risk individuals. Lifestyle intervention

programs usually aim for weight loss of at least 5% of total body-weight, which can be achieved

by following a healthier diet and exercising more frequently (Lindstrm et al, 2003).

Dietary Guidelines

A healthy diet is generally defined as having a total fat intake of less than 30% of daily

calories consumed and a fiber intake of at least 15 grams per 1000 calories consumed (Uusitupa

et al., 2003). Uusitupa et al. (2000) in the Finnish Diabetes Prevention Study (DPS) also

recommended that 50% of daily calories come from carbohydrates, less than 10% from saturated

fat, and that individuals should not consume more that 300 mg of dietary cholesterol per day.

Suggested foods in a healthy diet include whole-grains, fruits, vegetables, and lean meats

(Bazzano et al., 2005). Hu et al. (2001) agree with previous literature that type II diabetics and

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individuals at high risk for type II diabetes should eat a low-glycemic diet with increased

amounts of fiber. These researchers also recommend consuming non-hydrogenated

polyunsaturated fat and reducing and avoid trans-fatty acids in order to restore insulin sensitivity

(Hu et al., 2001).

Other studies have found that diets that emphasize monounsaturated fats instead of

saturated fats can be more effective in preventing and reversing insulin resistance. Their results

suggest that a diet that is rich in monounsaturated fats can improve glucose metabolism more

effectively than diets that emphasize either reduced-fat or polyunsaturated fat (Lindstrm et al.,

2003). Lindstrm et al. (2003) found that after a year of regular nutrition counseling, individuals

that were assigned to a lifestyle intervention group where they were told to follow specific

dietary guidelines had an average weight reduction of 4.5 kg, which is significant in comparison

to the average weight reduction of 1 kg in the control group. The common theme for dietary

changes to prevent or delay the onset of type II diabetes is to reduce the total number of calories

consumed, increase dietary fiber intake, and decrease cholesterol intake.

Exercise Guidelines

It has been well documented that even modest amounts of physical exercise have a

profound effect in preventing the development of type II diabetes by directly effecting the

reduction of visceral fat, body weight, blood pressure, lipid profile, and insulin resistance and by

improving glucose tolerance (Bazzano et al., 2005). However, exercise recommendations vary

widely and it is not clear if there is a preferred form of exercise for decreasing and preventing

type II diabetes. Uusitupa et al. (2003) suggest that exercise should consist of at least 30 minutes

of moderate intensity daily. Laaksonen et al. (2005) found that moderate-to-vigorous exercise

may be more beneficial for delaying type II diabetes than low-intensity exercise. Their study

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used participants from the DPS to determine which forms of activity and leisure-time physical

activity (LTPA) were most effective in reversing insulin resistance and lowering the risk of type

II diabetes in at-risk individuals. Laaksonen et al. (2005) noted that low-to-moderate intensity

aerobic exercise including walking, hiking, and cycling have been the traditional

recommendations for diabetic and prediabetic individuals, but that the benefits of resistance

training and high-intensity or interval training in type II diabetes prevention have become

increasingly evident. Together with the Center for Disease Control in Prevention in the U.S. and

the American College of Sports Medicine, Laaksonen et al. (2005) concluded that a minimum of

30 minutes of moderate-to-high intensity aerobic exercise or resistance training four to six days a

week had the most potent effects on type II diabetes and related metabolic syndrome.

Effectiveness of Lifestyle Modification Compared to Traditional Diabetes Medication

The Diabetes Prevention Program Research Group conducted a large, randomized clinical

trial in 2005 using adults in the U.S. who were categorized as high-risk individuals for the

development of type II diabetes (had a BMI >30 and high fasting blood sugar levels). The

purpose of the study was to determine whether lifestyle intervention or a popular diabetes

treatment medication (metformin a biguanide antihyperglycemic agent) had a stronger effect

on preventing the onset of type II diabetes. They concluded that lifestyle intervention had a

stronger effect on preventing type II diabetes than did drug intervention with metformin in

individuals at high risk (Diabetes Prevention Program Research Group, 2005). The results of

lifestyle changes were a decrease in blood glucose and lipid concentrations and a lower incidence

of type II diabetes. Lindstrm et al. (2003) had similar results in their study and found that

lifestyle intervention led to beneficial changes in diet, exercise, blood glucose, and lipid

concentrations and had a significantly reduced the incidence of type II diabetes.

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 Some type II diabetes patients attempt short-term rapid weight loss strategies in order to

improve their health and alleviate some of their diabetes symptoms. It is important to note that

short-term weight loss efforts are less effective for long-term glucose tolerance than slower, more

gradual but sustainable weight loss. Lindstrm et al. (2003) concluded that a small negative

energy balance sustained over a long period of time is more beneficial for reversing insulin

resistance and restoring glucose tolerance than more rapid weight loss strategies that emphasize

more drastic, short-term energy restriction.

Cummings et al. (2004) conducted a study on the effectiveness bariatric surgeries (which

are considered to be more of a short-term effort) on decreasing insulin resistance weight loss in

obese patients in comparison to steady, long-term weight loss strategies. The concluded that even

though many patients who underwent bariatric surgery experienced significant weight loss, this

weight lost did not have a strong effect on improving glucose homeostasis and reducing insulin

resistance, and many patients gained back much of the weight that was lost (Cummings et al.,

2004). These findings may be explained by the fact that bariatric surgery patients did not

necessarily change their lifestyle (exercise levels and dietary habits), which are known to have a

positive effect on glucose homeostasis and insulin sensitivity. Together with existing research,

these findings emphasize the notion that a lifestyle invention approach and steady, long-term

weight loss are highly effective forms of blood glucose and weight management that prevent the

development of type II diabetes in high-risk individuals.

Length of Effectiveness of Lifestyle Changes

One of the main questions raised about lifestyle intervention and its effectiveness in

treating type II diabetes is how long the benefits of lifestyle intervention and reduced rates of

chronic diseases last. It has been widely known from clinical research that lifestyle overhaul is an

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effective method for treating type II diabetes and other related chronic disease, however, the

duration of this success after the initial intervention is often vague or left out.

Li et al. (2008) conducted a 20-year follow-up study that focused on the long-term effects

of lifestyle changes in diabetes prevention. The goal of the study was to evaluate whether

lifestyle interventions have an enduring effect on the risk of diabetes, diabetes-related chronic

diseases, and ultimately mortality. Their aim was to produce results similar to those of the DPS

which is is one of the few studies that has previously addressed this question. The DPS reported

that the incidence of type II diabetes decreased for three years after the four-year intervention

program (Uusitupa et al., 2000).

The China Da Qing Diabetes Prevention Study (CDQDPS) was the first large-scale

clinical trial that studied the effect of different lifestyle interventions amongst people with

impaired glucose tolerance. In 1986, 577 adults with impaired glucose tolerance from 33 Chinese

clinics were randomly assigned to either one of three lifestyle intervention groups (diet, exercise,

and diet and exercise) or the control group. Intervention programs were carried out for six years

and ended in 1992. In 2006, participants were followed-up to evaluate the long-term effects of

the lifestyle intervention programs. The researchers were focused on the incidences of diabetes,

cardio-vascular disease (CVD), and mortality.

At the 20-year follow up point in 2006, the CDQDPS was able to reassess the effects of

lifestyle interventions on type II diabetes for individuals who were at high risk for 568 of the

original 577 participants (98%) (Li et al., 2008). They found that individuals in the diet and

exercise group had 51% lower incidence of type II diabetes compared to the control group during

the active intervention and 43% lower incidence compared to the control group at the end of the

20-year period. The average annual incidence of type II diabetes for 7% for individuals in the

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three intervention groups and 11% for individuals in the control groups. The cumulative

incidence after 20 years was 80% for the intervention groups and 93% in the control group, and

individuals in the intervention groups spent an average of 3.6 fewer years with type II diabetes

than individuals in the control group (Li et al., 2008). The findings of the CDQDPOS indicate

that group lifestyle interventions that are over 6 years in duration can prevent and delay the onset

of type II diabetes for at least two decades after the active intervention. These results are

consistent with those of the DPS, which found that the type II diabetes risk reduction for people

with impaired glucose tolerance without intervention stays high93% of their control group

developed type II diabetes over 20 years (Uusitupa et al., 2000).

Other studies with shorter follow-up periods have suggested that 5-10% of individuals

with impaired glucose tolerance develop diabetes annually, but that many are able to restore

normal glucose tolerance without undergoing major lifestyle interventions (Hu et al., 2001).

Tuomelheto et al. (2001) conducted a four-year follow-up study that also analyzed the effects of

lifestyle intervention focused on diet and exercise in prediabetic individuals. They measured

weight loss, blood glucose levels, and diabetes incidence after one year. Almost identical to the

results of Lindstrm et al. (2003), these researchers found that the intervention group lost an

average of 4.2 kilograms after the first year, which is highly significant in comparison to the

control group, which lost an average of 0.8 kilograms. At the two year follow up point, weight-

loss was still significantly greater in the intervention group than in the control group, with

averages loss of 3.5 kilograms and 0.8 kilograms respectively (Tuomelheto et al., 2001). At the

end of the study, type II diabetes was diagnosed in 11% of the intervention group and 23% of the

the control group, with an 58% overall decrease of diabetes incidence in the intervention group

compared to the control group. Tuomelheto et al. (2001), Li et al. (2008), and Uusitupa et al.

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(2000) all concluded that lifestyle intervention does delay and prevent the development of type II

diabetes in high risk individuals, however these findings were the most statistically significant

for Tuomelheto et al. (2001), which was a four-year follow-up study, in comparison to the other

two studies, which were both 20-year follow-up study. With this in mind, it is reasonable to

suggest that a longer study may yield more accurate results and that the strength of lifestyle

interventions lessens over time.

The discrepancy in findings between longer follow-up studies and studies that are

conducted for shorter time periods suggests that a longer time is needed to evaluate the

effectiveness of lifestyle intervention in preventing or delaying the onset of type II diabetes.

Studies of shorter duration may have stronger significance because participants are more recently

influenced by lifestyle intervention programs. These researchers conclude that based on the

success of group lifestyle intervention on the delay and prevention of type II diabetes in high-risk

individuals, a global adoption of this intervention strategy is relevant from a public health

standpoint because it could decrease the global diabetes death toll, which is over three million

people annually (Li et al. 2008).

Conclusion

Add a paragraph that summarizes studies (maybe a few ideas from each section), next

steps and suggested research clarification on dietary suggestions. KEEP IT FLOWING!

The main fi nding in the DPS was that

nonpharmacologic lifestyle intervention
of people at high risk for diabetes does
prevent or at least postpone the onset of
type 2 diabetes. The observed difference
in incidence between the intensive intervention
and the usual care control group
indicates that the intervention needs to be
individualized and continuing and performed
by skilled professionals in order

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to be effective. The lifestyle intervention
program used in the DPS is practical and
can be implemented

The preponderance of evidence reviewed here on risk factors

for and prevention of diabetes demonstrates that type 2
diabetes mellitus which comprises 95% of diabetes cases, is a
preventable disease. Because of the cost and morbidity of
diabetes and the rampant increase in overweight and obesity
and in incidence of diabetes in the U.S. population, prevention
of even a small part of the growing number of cases would save
thousands of lives and billions of health care dollars. One
inescapable conclusion is that the public health importance of
diabetes prevention is indisputable. To reduce the burden of
this devastating disease, prevention programs must target not
only the affected individuals but also families, workplaces,
schools, and communities.

Many of the studies discussed in this paper address the risk factors and prevention

methods for type II diabetes and have shown that in most cases it is a highly preventable and

reversible disease. The prevalence of obesity and type II diabetes in the U.S. has reached

epidemic proportions. Due to the high cost and morbidity of this disease, even small-scale

prevention could save billions of dollars and thousands of lives. It is indisputable that the public

health implications of type II diabetes prevention would significantly reduce both individual

suffering the burden that diabetes-related health care costs have on our society. As such, it is

critical that prevention programs target affected individuals and their families, as well as schools,

workplaces, and entire communities.

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I have neither given nor received unauthorized aid on this assignment.

M. Leopold

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