Pathophysiology and Treatment of Diabetes Type 2

Running head: PATHOPHYSIOLOGY AND TREATMENT OF DIABETES TYPE 2
PATHOPHYSIOLOGY AND TREATMENT OF DIABETES TYPE 2
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1PATHOPHYSIOLOGY AND TREATMENT OF DIABETES TYPE 2
Table of Contents
Definition...................................................................................................................................2
Epidemiology.............................................................................................................................2
Aetiology and Pathophysiology.................................................................................................3
Clinical Signs and Symptoms....................................................................................................7
Differential Diagnosis................................................................................................................7
Investigation...............................................................................................................................9
Orthodox Medical Treatment.....................................................................................................9
Natural Medicine......................................................................................................................11
Prognosis and Complications...................................................................................................13
Resource List............................................................................................................................14
References................................................................................................................................17

2PATHOPHYSIOLOGY AND TREATMENT OF DIABETES TYPE 2
Definition
Diabetes is a complex disorder of carbohydrate, fat, and protein metabolism which is
a result of a deficiency of insulin secretion by the beta cell of the pancreas or resistance to
insulin.This is a chronic condition that affects the way the body metabolises glucose causing
hyperglycaemia (Mosby 2017). Type 2 diabetes (T2D) was previously known as non-insulin
dependent and adult-onset diabetes mellitus and is the most common form-accounting for
about 90% of cases (Mayo Clinic 2019).
Epidemiology
International Diabetes Federation (IDF) has estimated, 451 million people among 18-
99 years of age, are affected with Diabetes in 2017, with a prevalence of 8.4% and speculated
that the rate of prevalence is likely to arise up to 9.9% by 2045 (Cho et al. 2018).
Epidemiological survey among populations of UK, found 90.4% of British population are
affected with type 2 diabetes with a prevalence rate of 4.5% (Holman, Young and Gadsby
2015). Occurrence of type 2 diabetes depends on several factors like obesity, glucose
tolerance, and high carbohydrate meal. Higher prevalence of diabetes type 2 has been found
among African women of sub-Sahara province, due to excess obesity (Mbanya et al. 2014).
Data suggests, an overall prevalence of 5.5% among men and 5.9% among women, regarding
diabetes type 2 (Hilawe et al. 2013). Type 2 diabetes has been found to be strongly related
with parental inheritance.
Furthermore, over the past decade, diabetes prevalence has risen faster in low and
middle-income countries than in high-income countries (WHO 2016).

3PATHOPHYSIOLOGY AND TREATMENT OF DIABETES TYPE 2
Aetiology and Pathophysiology
According to Ross and Wilson (2018), the onset of type 2 diabetes is gradual and it
frequently goes undetected until signs are found on routine investigations or a complication
occurs. The causes are multifactorial and predisposing factors include:
 Obesity
 Sedentary lifestyle
 Increasing age, predominantly affecting middle-aged and older adults
 Genetic factors
 Gestational diabetes
Obesity is one of the major contributing factors of type 2 diabetes. Adiponectin, a
hormone produced especially by adipocytes, regulates insulin sensitivity. Adiponectin
activates AMPK (AMP-activated protein kinase), which phosphorylates downstream targets,
ultimately stimulating ‘Eat’ response or appetite, glucose uptake, glycolysis and inhibiting
biosynthesis of fatty acids. In patients with obesity and type 2 diabetes, adiponection
mediated AMPK response is altered along with decreased glucose tolerance, causing a rise in
blood glucose level. Hence, type 2 diabetes results in slower removal of glucose from
circulatory blood and cells become insulin-insensitive developing hyperglycemia (Breslavsky
et al. 2013).
Mayo Clinic (2019), the risk of type 2 diabetes increases with age, mostly because
people tend to exercise less, lose muscle mass and gain weight as they age. Physical activity
helps to control an individual's weight, uses up glucose as energy and makes the cells more
sensitive to insulin.
Epigenetic study by Omar (2013) elicited that risk of T2D is approximately 40% in
case one of the parent has type 2 diabetes, and chances increases to 70% if both parents have

4PATHOPHYSIOLOGY AND TREATMENT OF DIABETES TYPE 2
the same. Study suggests, monozygotic twins have a 60-70% concordant chance of
developing T2D, where both the parents have T2D (Kaprio et al. 1992). Several hereditary
genes like peroxisome proliferator-activated receptor gamma (PPARG), insulin receptor
substrate 1 and 2 (IRS-1, IRS-2), HNF-1A, HNF-1B, TP53 are associated with progression of
type 2 diabetes (Gaulton et al. 2008; Kung, Basu and Murphy 2016).
Anti-diabetic drugs, such as Metformin, which is widely used for T2D treatment, can
exert several side effects in humans. Most significant of them is hypoglycemia or insulin
shock. A lowered blood glucose level and higher intracellular glucose is typically associated
with drug-induced hypoglycemia. Glucose is the principal source of energy for functioning of
brain. Hence, hypoglycemia can affect by lessening energy supply to the neurons, leading to
a variety of health complications like depression, coma, seizure, arythmia or irregular
heartbeat, myocardial ischemia, and even death (Goldstein and Müller-Wieland 2016). A case
study by Al-Abri et al. (2013) has found, metformin overdose causes lactic acidosis including
decreased glucose production and absorption in liver.
Proper diet is another factor corresponding T2D manifestation. People with no
breakfast or poor breakfast are likely to develop type 2 diabetes, in contrast to those who
have proper breakfast daily, due to higher food intake during lunch. These candidates have
higher Body Mass Index (BMI), which could contribute into obesity, thus T2D (Mekary et al.
2013).
Several studies have demonstrated that women who have had gestational diabetes
have a 20% to 50% increased risk for developing type 2 diabetes later in life.

5PATHOPHYSIOLOGY AND TREATMENT OF DIABETES TYPE 2
Fig.1 http://www.patiadiabetes.com/en/
In diabetes type 2, body cells are unable to extract glucose from the extracellular fluid and
there are 2 main reasons for this:
 Inadequate insulin levels means that activation of the insulin mediated glucose
transport mechanisms in the plasma membrane is deficient.
 Insulin receptors on the cell surface may become dysfunctional, so even in the
presence of normal or elevated blood glucose, the cells cannot extract the insulin they
require.