Blood Sugar Regulation (week 2)

Question 1

Incidence of type 2 diabetes

Answer 1

in the US:
-top 10 leading cause of death
-37.2 million (11.3% of total population)
-48.8% in adults 65+
-96 million with prediabetes
-1 in 2 adults with diabetes or prediabetes

global incidence:
-increased from 108 million in 1980 to 422 million in 2014 (4x increase in 34 years)
-in 2019, ~463 million adults with diabetes
-estimated to rise to 700 million by 2045

changing names:
-type 1 diabetes historically called “juvenile diabetes”
-type 2 diabetes historically called “adult onset diabetes”
-age based names are no longer accurate due to the rising incidence of type 2 diabetes in children

Question 2

insulin resistance

Answer 2

insulin resistance = a condition in which cells in the body become less responsive to the effects of insulin
-insulin receptors on target cells lose sensitivity to insulins signals
-pancreas produces more insulin to compensate

over time, results in:
-hyperglycemia (chronically elevated blood sugar levels)
-hyperinsulinemia (chronically elevated blood insulin levels)
-pancreatic beta cells may not produce sufficient insulin

associated with:
-high blood pressure
-weight gain (excess abdominal or visceral fat)
-hormonal dysregulation
-inflammation
-fatigue

Question 3

glucose intolerance

Answer 3

related to insulin resistance, but is a broader term

refers to the body’s inability to process and metabolize glucose effectively, including:
-prediabetes
-diabetes

insulin resistance is a key factor in developing glucose intolerance

to summarize:
-insulin resistance = decreased responsiveness of cells to insulin
-glucose intolerance = body’s inability to process and metabolize glucose

Question 4

glycation

Answer 4

chemical reaction - glucose molecules in the bloodstream bind to proteins or lipids

forms “advanced glycation end products” (AGEs) which accumulate in tissues over time
-AGEs cause damage to cells by reacting to essential proteins

considered to be irreversible

accelerates the aging process

promotes inflammation and oxidative stress

note that BOTH chronically elevated glucose AND sharp glucose spikes contribute to the glycation process

HbA1c measures glycation of red blood cells

Question 5

Glucose ranges

Answer 5

healthy blood sugar range:
-fasting blood glucose: (8hr after eating) below 100 mg/dL
-lower risk at 70-90 mg/dL
-postprandial blood glucose: (2 hrs after eating): below 140 mg/dL

Prediabetes:
-impaired fasting glucose (IFG): fasting blood glucose levels between 100 to 125 mg/dL
-impaired glucose tolerance (IGT): two hour postprandial blood glucose levels between 140 to 199 mg/dL

Diabetes:
-fasting blood glucose: above 125 mg/dL on more than one occasion
-post prandial blood glucose: equal to or above 200 mg/dL on more than one occasion
-oral glucose tolerance test (OGTT): two hour postprandial blood glucose equal to or above 200 mg/dL during an oral glucose tolerance test
-HbA1c: equal to or above 6.5% on more than one occasion

Question 6

Stages of Dysglycemia

Answer 6

1. reactive hypoglycemia
2. insulin resistance & hyperinsulinemia
3. metabolic syndrome & pre-diabetes
4. type 2 diabetes

Question 7

healthy glucose regulation

Answer 7

insulin (+incretins) help limit upper range “use & store”

glucagon and adrenal hormones help limit lower range “release storage”

key characteristics: glucose stays within range, smooth curves, metabolic flexibility, and stable energy

Question 8

Stage 1: reactive hypoglycemia

Answer 8

in the early stages of dysglycemia, we begin to see sharp swings in blood glucose.

When we consume a high glycemic meal, our blood glucose shoots up past normal, healthy upper ranges.

It is moving so fast that the body produces excessive amounts of insulin to protect you from the damages of hyperglycemia.

The body does not know when this rapid increase in glucose will end, so it basically overcorrects by producing excessive amounts of insulin.

Once the glucose consumption stops, the high insulin levels continue to do their work, shuttling glucose into cells.

This causes a sharp drop in blood glucose, called reactive hypoglycemia.

Question 9

Stage 1: reactive hypoglycemia

Answer 9

With these early stages of dysglycemia, our cellular insulin response is still working well, and so
our fasting glucose levels are still returning to normal most days.

This is more of a rollercoaster ride, with sugar highs and crashes rather than constantly elevated glucose, but over the long term, it can contribute to the progression of later stages of dysglycemia.

One of the things that make the rollercoaster so taxing is that the adrenal glands are required
to help keep the floor from falling out below us.

The increased levels of stress hormones can
cause jittery feelings and anxiety, commonly referred to as being “hangry.”

So, when we talk about low blood sugar being a form of biochemical stress, this kind of reactive hypoglycemic
spell is exactly what we are talking about.

Question 10

Hypoglycemia signs and symptoms

Answer 10

• Increased cravings for sugar and refined carbohydrates
• Increased blood pressure
• Unstable energy levels
• Headaches
• Mood swings
• Anxiety
• Disrupted sleeping
• Ravenous hunger
• Feeling light-headed if meals are missed
• Feeling jittery or shaky between meals
• Sweating
• Rapid or irregular heartbeat
• Reduced cognitive performance

Question 11

Stage 2: Insulin Resistance & Hyperinsulinemia

Answer 11

decreased response to insulins signal

sugar highs: crashes may become less frequent

accumulation of glucose and insulin = hyperglycemia and compensatory hyperinsulinemia

chronically elevated glucose leads to glycation

chronically elevated insulin contributes to:
-elevated blood pressure
-dyslipidemia
-inflammatory conditions
-hormonal dysregulation
-fatigue
-weight gain

Question 12

Stage 2: Insulin Resistance & Hyperinsulinemia

Answer 12

fatigue & weight gain:
-two of the most common complaints
-signs that blood glucose regulation is not optimal

weight gain:
-lipolysis is inhibited, lipogenesis is stimulated
-lipid overflow hypothesis = when body fat stores are maxed, lipids are stored as visceral fat around organs

fatigue:
-glucose uptake is impaired = cells do not receive adequate energy supply = fatigue and low energy levels
-low energy can lead to reduced activity

Question 13

Stage 2: Insulin Resistance & Hyperinsulinemia

Answer 13

insulin resistance may be seen as a protective mechanism for cells:

-glycolysis in mitochondria produces oxidative stress, a normal cost of producing energy

-insulin resistance could be considered as an antioxidant defense mechanism to prevent cells from excessive oxidative damage

Question 14

Stage 2: Insulin Resistance & Hyperinsulinemia

Answer 14

Common signs and symptoms of insulin resistance include:

• Increased hunger
• Increased fatigue and lethargy
• Increased brain fog and difficulty focusing
• Increased weight gain, especially in the abdomen
• Increased blood sugar
• Increased triglycerides and cholesterol levels
• Increased blood pressure
• Hyperpigmentation of the skin, especially around the neck and in the armpits
• Depression and mood disorders
• Endocrine imbalances, including thyroid and fertility issues
• Slow healing
• Premature aging

Question 15

Stage 3: Metabolic Syndrome and Prediabetes

Answer 15

share common features and often coexist, but have distinct characteristics

metabolic syndrome = a set of specific biometrics

prediabetes = elevated blood glucose levels below the diagnostic criteria for diabetes

Prediabetes is diagnosed when either of the following criteria is met:
* Impaired fasting glucose (IFG): Fasting blood glucose levels between 100 mg/dL and 125 mg/dL.
* Impaired glucose tolerance (IGT): Blood glucose levels measured two hours after
an oral glucose tolerance test (OGTT) between 140 mg/dL and 199
mg/dL

Question 16

Metabolic syndrom

Answer 16

a cluster of interconnected metabolic abnormalities

an increased risk of cardiovascular disease and type 2 diabetes

criteria for diagnosis:
* Abdominal obesity: Waste Circumference > 40” male / 35” female
* Elevated triglycerides (>150mg/dL)
* Blood Pressure (>130/85 mm/Hg)
* Elevated fasting glucose (> 100mg/dL)
* HDL below 50 mg/dL

additional signs include:
-systemic inflammation
-reproductive hormone dysregulation

Question 17

Stage 4: Type 2 Diabetes

Answer 17

persistent hyperglycemia

insulin production insufficient to compensate for insulin resistance

impaired insulin secretion from pancreas

in some cases, exogenous insulin is required, or medication to:
-potenize insulin signaling
-lower glucose absorption in the intestines
-increase glucose excretion

Diagnostic criteria:
-Elevated blood glucose levels (at least one reading above 200 mg/dl in 24 hours)
-Hemoglobin A1c (HbA1c) above 6.4

Question 18

Stage 4: Type 2 Diabetes

Answer 18

Common signs and symptoms of Type 2 Diabetes include:

• Extreme hunger or thirst
• Persistent hunger, even after a meal
• Frequent or increased urination
• Tingling sensations in the hands or feet
• Chronic, persistent fatigue
• Frequent infections

a chronic condition:
-effects can be mitigates through diet and lifestyle
-some individuals can achieve remission or reversal
-clients on glucose lowering medications need to work with prescribing physician to manage medication and prevent hypoglycemia

Question 19

Type 1 diabetes

Answer 19

autoimmune condition

destruction of pancreatic beta cells (insulin)

uncontrolled elevations of blood sugar

requires insulin medications

permanent condition with no known cure

diet and lifestyle modifications can help manage disease and reduce complications

influencing factors:
-genetic predisposition (HLA class II genes)
-environmental factors include early life nutrition
-A1 beta-casein in cows milk

increasing rates:
-2% ride in T1D in youth (<20 per year)
-28% more US citizens compared to 2017

Question 20

glycemic index (GI)

Answer 20

measures how quickly a carbohydrate containing food raises blood glucose levels, compared to a reference food

reference food = pure glucose or white bread

how is it obtained?
-blood glucose after consuming enough of the food to equal 50g of available carbohydrate (sugar and starch)
-GI number = a comparison between the glycemic response to a specific food vs the reference food on a scale of 0-100
-reference food = GI of 100

Question 21

glycemic index (GI)

Answer 21

high GI = 70 or above
-rapidly digested and absorbed = quick and significant increase in blood sugar levels

ex: white bread, white rice, sugary beverages, most processed snacks

Low GI = 55 or below
-digested and absorbed more slowly = slower and smaller rise in blood sugar levels

Ex: meat, fermented dairy, most tart fruits and veggies, whole grain, legumes, nuts

Question 22

glycemic index limitations

Answer 22

GI values do show:
-the speed at which glucose enters the bloodstream from 50g available carbohydrate

GI values don’t show:
-how many grams of carbohydrates are found in a serving

why is this a problem?
-GI can wrongly malign foods which require extremely large servings to reach 50g of available carbohydrates:

-1.5 pounds of carrots (one large bag) = 50g of carbohydrates (much more than one serving)
-one large single carrot weighs about 0.2 pounds (low glycemic impact)

Question 23

glycemic load (GL)

Answer 23

what is it:
-a more contextualized rating of a food’s impact on blood glucose
-multiplies a given foods GI by the number of non-fiber carbohydrates (in grams) contained in a single serving size

-low GL = 10 or less
-moderate GL = 11-19
-high GL = 20 or more

ex: carrots (peeled and boiled in salt water) = GI of 92, but GL is only 9 (considered low)

Question 24

Refined vs Whole Grain

Answer 24

the more processed a food is, the higher its GI will be

ex: “quick oats” vs steel cut or old fashioned rolled oats

refined cereal grain flours have a higher GI
-lack the bran and endosperm (vitamins, minerals, phytochemicals, and healthy fats)

reducing/avoiding products made from refined flour is a powerful way to improve blood glucose management

Question 25

fermentation

Answer 25

sourdough: lactic acid bacteria and yeast transform sugars and starches into:
-carbon dioxide (causes bread to rise)
-lactic acid
-acetic acid

reduces the amount of available starch

organic acids slow absorption:
-lactic acid = inhibition of amylase enzymes
-acetic acid = delays gastric emptying rate

regular white bread = GI of 100 and GL of 10

sourdough whole wheat bread = GI of 54 and GL of 8

GI < 55 is defined as low, 56-69 is moderate, and >70 is high

Question 26

glycemic index: cooking methods

Answer 26

boiled sweet potato vs baked sweet potato

moisture content:
boiled sweet potato = cooked in water, water softens and gelatinizes the starch, lower GI

baked sweet potato = cooked in dry air, reduces the water content, higher GI

cooking time:
boiled sweet potato = shorter cooking time, preserves structural integrity of carbohydrates, lower GI
-baked sweet potato = longer cooking time, breaks down the starch further, higher GI

note: most foods have a lower GI when consumed raw

Question 27

GI & GL practical tips

Answer 27

carbohydrates eaten with fats = lower GI

fiber content = lower GI (eat whole foods)

the more cooked or processed the food, the higher the GI

foods high in fructose and artificial sweeteners may have misleadingly moderate GI:
-fructose must first be converted to glucose to be ,easured
-fructose still enters the bloodstream and causes glycation

response to carbohydrates is highly bioindividual based on:
-microbiome
-hormones
-activity levels

GL is more useful tool than GI alone

Question 28

Total vs Net carbohydrates

Answer 28

total carbohydrates:
-the sum of all types of carbs present
-includes sugars (naturally occurring and added), fiber, and starch
-lumps together glycemic and non-glycemic carbs
-listed on nutrition labels

net carbohydrates:
-SUBTRACTS the fiber from the total carbohydrates
-more accurate number
-not always listed on food labels

The formula for calculating net carbs is usually:

Net Carbs = Total Carbohydrates - Dietary Fiber

Question 29

microbiome profiles

Answer 29

exact microbial profile in patients with blood glucose dysregulation is not fully understood

distinct differences do exist

“metabolic endotoxemia” = increased adiposity and systemic inflammation result from chronic exposure to lipopolysaccharide

studies show alterations in the gut microbiome in T2DM, T1DM, and those on the brink of developing T1DM

Question 30

microbiome and insulin resistance

Answer 30

dysbiosis contributes to:

inflammation: lipopolysaccharide impairs insulin signaling and promotes systemic inflammation

barrier dysfunction: increased passage of harmful substances into bloodstream

elevated zonulin: found in patients with T1D preceding/during disease

short chain fatty acids: dysbiosis disrupts production of butyrate

disrupted bile acid metabolism: dysbiosis alters secondary bile acid metabolism by bacteria

impaired gut hormone regulation: reduced production of GLP1 and PYY can impair insulin secretion and reduce insulin sensitivity

production of metabolites: elevated levels of metabolites some associated with insulin resistance (trimethylamine N-oxide, TMAO)

Question 31

firmicutes to bacteroidetes ratio

Answer 31

two major phyla of bacteria

mixed research results in GI disorders and metabolic disorders

firmicutes extract more energy from food = hypothesis that elevated firmicutes to bacteroidetes ratio is marker of metabolic disorders

in contrast:
-several studies have not observed significant changes in ratio
-some show decreased firmicutes/bacteroidetes ratio associated
-bacteroides includes largest group of gram negative bacteria, conflicting with the elevated firmicutes hypothesis

Question 32

microbiome takeaways

Answer 32

relevance of firmicutes and bacteroidetes is unclear

loss of diversity and high levels of gram negative bacteria can contribute to insulin resistance and blood sugar dysregulation

anything that contributes to alterations in the microbiome could potentially contribute to disturbance in metabolism and glucose regulation

clinical trials using some probiotics show benefits to glucose, lipids, blood pressure, and inflammatory markers in metabolic syndrome and T2D

Question 33

A1 vs A2 beta-casein

Answer 33

A1:
-most cows produce both A1 and A2 beta-casein
-contains histidine at position 67
-histidine allows cleavage by proteolytic enzymes
-releases the peptide beta-casomorphin 7 (BCM-7)
-BCM-7 binds/activates opiois receptors in CNS, GI tract, and some immune cells
-may inhibit immune function or trigger inflammatory immune reactions
-increased absorption of BCM-7 in infants

A2:
-sheep and goat milk. certain herds of cows of african, asian, and european descent
-human breastmilk
-contains proline at position 67
-proline resists hydrolysis and cleavage of enzymes

Question 34

A1 beta-casein milk and risk of T1D

Answer 34

Mu-opioid receptors found in islets of langerhans (pancreas - insulin)

BCM-7 from A1 beta casein can disrupt pancreas function

differences in dietary intake of cow dairy among populations = primary factor associated with varying rates of T1D

19 country study:
-finland and sweden = highest incidence of T1D and highest rate of A1 beta-casein consumption per person
-venezuela and japan = lowest incidence of T1D and lowest rate of A1 beta-casein consumption per person

systemic review and meta-analysis of 96 studies: what dietary factors reduced the risk of T1D?
-breastfeeding for 6-12 months
-avoiding dairy and gluten for the first 3 months of life
-reducing exposure to cows milk in early childhood

population based cohort studies:
-children who were never breastfed = 2x risk of T1D compared to children breastfed for 12 months
-children with mild-moderate dairy intolerance: acute GI symptoms, markers of inflammation, markers of immunity increased with A1 but not A2 beta-casein
-in adults aged 25-68, A1 beta-casein was associated with more GI symptoms, stomach inflammation, discomfort, levels of BCM-7, reduced transit time, cognitive functioning, and levels of short chain fatty acids

Question 35

T1D vs T2D Prevalance

Answer 35

CDC estimates that in the US:
-T1DM = ~0.55% representing 1.6 to 1.9 million
-T2DM = ~11.3% representing 37.2 million, not counting millions with other stages

Question 36

circadian rhythms

Answer 36

24 hour internal clocks

central control in hypothalamus, peripheral clocks in other organs

influenced by environmental factors like light and temperature

circadian rhythm genes influence glucose regulation. production of melatonin in the evenings causes insulin resistance and impairs the release of insulin by the pancreas

Question 37

melatonin

Answer 37

synthesized and secreted by the pineal gland

one of the most reliable markers of circadian rhythms

regulated by the hypothalamus

main types of melatonin receptors:
-MT1 and MT2 receptors: found in the islets of langerhans of the pancreas (insulin and glucagon)

melatonin inhibits the cAMP pathway in the pancreas:
-blocks insulin secretion from pancreas in later part of the day and evening

eat in line with the circadian rhythms of metabolism

having a late dinner is associated with an increased risk for diabetes

Question 38

chrononutrition

Answer 38

chrononutrition = how meal timing, metabolism, and circadian rhythms interact to influence health

before the industrial revolution:
-moderate breakfast
-dinner was main meal in the midday
-supper was light or option in evening
-snacking was far less common

after the industrial revolution, people worked away from home as more career opportunities arose, and electric lights made staying up late more compelling
-breakfast became an optional meal, often skipped
-midday meal became lunch and was lighter fare
-in the evening, dinner became the main/largest

modern trends:
-carb heavy breakfast on the go, large evenings meals, late night snacking

Question 39

chrononutrition

Answer 39

studies show:
=when comparing identical meals given in evening or morning, evening meal resulted in higher glycemic response in blood sugar

making breakfast the largest meal of the day and dinner the smallest meal is linked to:
-improved glucose tolerance and insulin function
-lower BMI
-decreased change of become overweight/obese
-reduced inflammation

Question 40

meal frequency

Answer 40

metabolic benefit in consuming 2-3 meals per day vs many small meals or snacks:
-greater insulin sensitivity
-reduction in BMI
-reduction in fat accumulation in the liver

fewer meals = give the body a window of low insulin exposure so we can utilize stored glucose for energy

intermittent fasting: extend fasting window in evening rather than morning aligns more with circadian rhythms

eat breakfast like a king, lunch like a prince, and dinner like a pauper

Question 41

inadequate sleep

Answer 41

inadequate sleep, late sleep timing, artificial exposure to light, and shift work are associated with metabolic dysfunctions such as type 2 diabetes

as sleep duration decreases, stress hormones increase, which contributes to blood sugar dysregulation

studies show:
-one week of 4-5 hours of sleep a night, cells became unresponsive to insulins signals
-animal studies: mice experience increase in adiposity and diabetes when kept awake during sleep window

Question 42

irregular sleep patterns

Answer 42

shift work increasingly common in the US (15-20% of workforce):
-irregular and prolonged hours
-exposure to artifical light
-abnormal sleeping patterns

overnight shift work:
-dysregulation of circadian rhythms
-reduced glucose tolerance
-increased risk of diabetes

meta-analysis that included 12 studies and 226,652 participants found that shift work
is strongly associated with an increased risk of developing type 2 diabetes.

One study included in this meta-analysis followed a large number of nurses for 20 years and kept track of their frequency of working night shifts. Having this kind of long-term research study adds a lot of strength to the findings since many of these metabolic impacts play out over time. And there are other large studies that back up this finding.

One study in the UK that looked at 272,214
participants also found that night shift workers were more likely to have type 2 diabetes than day workers.

Question 43

chronic stress

Answer 43

activation of the sympathetic nervous system (stress) activates cortisol, adrenaline, noradrenaline

cortisol triggers gluconeogenesis, raises glucose

cells of muscles and liver become insulin resistant in times of stress
-muscle cells can overcome this through insulin independent glucose transport stimulated by exercise

modern stress is not accompanied by exercise to counteract increase in glucose

studies show:
-moderate to high stress levels associated with 2.3x increase in developing T2D

elevated cortisol associated with:
-increased glucose levels
-decreased insulin sensitivity
-development of chronic disease including T2D

Question 44

hyperinsulinemia and stress response

Answer 44

high blood glucose and high insulin stimulate the sympathetic branch of ANS

excess simple carbohydrate ingestion = increased sympathetic nerve activity

changes linked to hyperinsulinemia

dose dependent relationship between insulin and noradrenaline in hyerinsulinemic state

not all carbohydrate consumption causes this reaction

Question 45

physical activity

Answer 45

physical activity = muscles use glucose for energy = improved glucose regulation

muscle contractions during exercise help transport glucose to skeletal muscles through insulin independent activation of GLUT4, even with insulin resistance

Question 46

sedentary lifestyle

Answer 46

physical inactivity linked to insulin resistance due to:
-gene expression
-reduced functioning of pancreatic beta cells
-reduced energy expenditure
-increased free radicals and oxidative stress
-increased low-
grade inflammation
-changes in sex steroid expression
-impairment in mitochondrial function.

Question 47

endocrine disrupting chemicals

Answer 47

rise in use of toxic chemicals

contributes to blood sugar dysregulation

“diabetogens”
* Bisphenol A (BPA)
* Persistent Organic Pollutants (POPs)
* Phthalates
* Perfluorinated Chemicals (PFCs)
* Glyphosate
* Arsenic & Heavy Metals
* Air Pollution

Question 48

chemicals of concern

Answer 48

Bisphenol A (BPA) - BPAs have been shown to alter insulin secretion, block insulin receptor sites.

POPs - Persistent Organic Pollutants (POPs) have also been shown to disrupt
blood glucose regulation48. Studies have found that individuals with the highest levels of POPs have a 12 times increased risk of developing Type 2 Diabetes.

Phthalates - Phthalates have been shown to disrupt blood glucose control and increase the risk of developing Type 2 Diabetes as well.

Perfluorinated Chemicals (PFCs) – Similar associations have been found with
higher levels of PFCs.

Question 49

chemicals of concern

Answer 49

Glyphosate - Recent studies in mice found that animals exposed to glyphosate experienced alterations in their carbohydrate and glucose metabolizing enzymes and a rise in proinflammatory biomarkers. Researchers found that glyphosate decreased the expression of
insulin receptors and GLUT2 glucose transporter in cell membranes.

Arsenic: There is also a strong link between arsenic levels in the body and the risk of diabetes. This is thought to be due to arsenic’s ability to damage beta cells of the pancreas, which results in a decreased production of insulin.

Heavy Metals: Similarly, heavy metals like lead, mercury, and cadmium are environmental pollutants that can accumulate in the body and adversely affect
glucose metabolism by a variety of mechanisms.

Air Pollution: Exposure to air pollution, particularly fine particulate matter
(PM2.5) and traffic-related pollutants, has been linked to insulin resistance and an increased risk of Type 2 Diabetes.

Question 50

thyroid conditions

Answer 50

association between hypothyroidism (low levels of thyroid hormones) and insulin resistance

thyroid hormones:
-help maintain viability and growth of beta cells (insulin)
-regulate insulin receptor expression and function
-influence lipid metabolism in the liver and peripheral tissues
-in hypothyroidism, circulating lipids increase and can interfere with insulin signaling = insulin resistance

leptin:
-tells the brain we have adequate energy stores and reduces the appetite
-hypothyroidism promotes leptin resistance

reduced thyroid hormone levels negatively affect mitochondrial activity = decreased cellular energy production and insulin resistance

Question 51

genetics

Answer 51

over 120 genetic variants linked to T2D

peroxisome proliferator-activated receptor gamma (PPARg gene)

pro12la variant of PPARg influences T2D susceptibility

diets higher in PUFAs that SFAs = Pro 12Ala expression is protective against T2DM

diets higher in SFAs than PUFAs = variant not considered protective

diet + genes = epigenetics

over expression of certain genes in the liver can lead to abnormally high levels of gluconeogenesis