Type 2 Diabetes Mellitus

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DEFINITION

Diabetes mellitus (DM) is a chronic metabolic disorder characterised by fasting

hyperglycaemia and disturbances of carbohydrates, fat and protein metabolism, with
a greatly increased risk of heart disease, nephropathy, retinopathy and other
complications. (WHO, 2019).

Two main types of DM are type 1 diabetes mellitus and type 2 diabetes mellitus
(T2DM). (WHO, 2019).

T2DM, previously called adult-onset or non-insulin-dependent diabetes (NICE,

2024), is characterised by insulin resistance (diminished tissue responses to insulin)
and insulin deficiency (where pancreas is unable to secrete enough insulin to
compensate for the deficiency), as well as an excessive or inappropriate glucagon
secretions, resulting in persistent hyperglycaemia. (Khardori, 2024; NICE, 2024).

The National Institute of Health and Care Excellence [NICE], (2024) defines
persistent hyperglycaemia as:
 HbA1c of 48mmol/mol (6.5%) or more
 Fasting plasma glucose level of 7.0mmol/L or more
 Random plasma glucose of 11.1mmol/L or more in the presence of signs and
symptoms of diabetes.

Poorly managed chronic elevated blood glucose leads to microvascular,

macrovascular and neuropathic complications. (Khardori, 2024).

EPIDEMIOLOGY

 10.7% of adult global population have diabetes, and there are approximately
537 million adults (20-79 years) living with the disease. It is projected that 786
million people will be diagnosed with the disease by 2045, a 46% rise. (IDF
Diabetes Atlas, 2021; Khardori, 2024).
 4.3 million people in the UK live with diabetes, with estimation of another
850,000 yet to be diagnosed, and 90% of all diagnosis are of T2DM.
(Diabetes UK, 2024).
 Worldwide, an estimated 17.7 million more men than women have DM.
(Kautzky-Willer, Leutner and Harreiter, 2023)

Figure 1: Estimates of comparative diabetes prevalence rates (20-79 years):

 Reference: IDF Diabetes Atlas, 2024.

 People of Asian, Chinese, Black African and Black Caribbean ethnicities have
been found to be 2-4 times more likely to have diabetes than White
populations, and are more likely to develop T2DM at a lower weight threshold.
(Diabetes UK, 2024).

 Age: The prevalence increases in those over 40. (IDF Diabetes Atlas, 2021).

 Incidences are increasing rapidly in other age groups. In America,

approximately 28% of adolescents between 12 and 19 years had T2DM in
2018. (Khardori, 2024).

 Diet: The rise in prevalence is almost 4x in developing countries due to

adopting ‘western lifestyles’ and rise in the obesity and overweight individuals.
(Reid, Bain and Kanamarlapudi, 2021). Africa, the Middle East and Southeast
Asia are predicted to have the highest increases. (Khardori, 2024).

AETIOLOGY
The aetiology of T2DM is a complex interplay of genetic, environmental and lifestyle
factors, each contributing to the development and the progression of the disease.
(Mambya et al., 2019).

Major risk factors for T2DM are:

 Age over 45, noting that the incidence is rapidly increasing in younger
individuals
 Obesity and overweight, BMI over 25 kg/m2
 Increased waist/hip ratio
 Family history of T2DM in a first-degree relative (sibling or parent)
 Hispanic, Native American, African American, Asian American or Pacific
Islander descent
 History of previous impaired fasting glucose or glucose tolerance test
 Hypertension (>130/80 mm Hg) or dyslipidaemia (HDL cholesterol level <40
mg/dL or triglyceride level >150 mg/dL)
 History of gestational diabetes or delivery of baby weighing more than 9lb
 Polycystic ovarian syndrome (which results in insulin resistance (IR))
 Low levels of adiponectin, elevated levels of fasting insulin
 Sedentary lifestyle
 Alcohol intake, smoking
 Socioeconomic disadvantage
(References: WHO, 2011; Pizzorno, Murray and Joiner-Bay, 2016; Galicia-Garcia et
al., 2020; Khardori, 2024).

Obesity
 80-90% of T2DM patients are obese (body mass index above 30 kg/m2).
(Reid, Bain and Kanamarlapudi, 2021).
 Obesity is characterised by elevated levels of cytokines and fatty acids,
provoking insulin resistance. (Reid, Bain and Kanamarlapudi, 2021).

Prediabetes
 The intermediate state between normal glucose tolerance and
hyperglycaemia. 5-10% progress to T2DM each year. (Reid, Bain and
Kanamarlapudi, 2021).

Genetics
 T2DM is a result of interaction between multiple genes and environmental
factors. Two genes, CAPN10 and TCF7L2, were reliably identified as being
associated with T2DM. (Ali, 2013; Torkamani, 2022).

Physical Activity
 A sedentary lifestyle increases proinflammatories (such as interleukin-6, C-
Reactive protein, etc), causing metabolic inflammation, which in turn leads to
inhibition of -cells function. (Galicia-Garcia et al., 2020).
Drug Treatments
 Statins, corticosteroids and thiazide diuretic and beta-blocker combined
treatment increase the risk of developing hyperglycaemia and T2DM (impair
insulin secretion and/or production). (Mayer-Davis et al., 2018; NICE, 2024).

Persistent Organic Pollutants (POPs)

 Elevated POP exposure has diabetogenic effect, by blocking of insulin
receptor sites and impairment of insulin production. (Mambiya et al., 2019).

PATHOPHYSIOLOGY

Excessive calorie intake leads to accumulation of triglycerides in the adipose tissue,

promoting hypertrophic enlargement of adipocytes. This causes the release of
proinflammatory cytokines leading to chronic low-grade inflammation. These
proinflammatory cytokines, together with free fatty acids (FFA), from additional
lipolysis of triglycerides in adipocytes, activate pathways which impair insulin
signalling, leading to IR. (Lima, Moreira and Sakamoto-Hojo, 2022).

Figure 2: Insulin stimulation of hypertrophic adipose tissue promotes

abnormal metabolic functioning:

Reference: Galicia-Garcia et al. 2020, p.14, Figure 4.

The main contributors to impaired insulin signalling are several cellular and
molecular mechanisms mainly mediated by oxidative stress, chronic low-grade
inflammation, mitochondrial dysfunction and endoplasmic reticulum stress. (Lima,
Moreira and Sakamoto-Hojo, 2022).

In response to IR, pancreatic -cells, in order to maintain metabolic homeostasis,

increase their secretion of insulin and/or their numbers. (Reed, Bain and
Kanamarlapudi, 2021).

Elevated glucose and FFA cause glucolipotoxicity in pancreatic -cells. Inflammation

and oxidative stress follow, leading to the loss of cell integrity. Oxidative stress leads
to inhibited movement of Ca2+, impairing insulin exocytosis from -cells.
(Galicia-Garcia et al. 2020).

During prediabetes, pancreatic -cells number and function decline slowly and it can
take up to 12 years before T2DM manifests. (Reed, Bain and Kanamarlapudi, 2021).

Ultimately, intricate interplay between pancreatic -cell dysfunction, increased

pancreatic -cell function and peripheral tissue IR, results in:
 Hyperglycaemia, due to impaired peripheral glucose uptake
 Dyslipidaemia (hypertriglyceridemia and low high-density lipoprotein [HDL]-
cholesterol), due to impaired fat intake
 Impaired amino-acid uptake and ATP production into peripheral tissues, such
as skeletal muscle, due to the impaired nutrient uptake and
 Disrupted balance between  and -cells leading to hyperglucagonemia.
Glucagon acts on liver to increase blood glucose levels, which further
amplifies hyperglycaemia and hyperlipidaemia.
(References: Galicia-Garcia et al., 2020; Reed, Bain and Kanamarlapudi, 2021;
Khardori, 2024).

Glucagonlike peptide-1 (GLP-1), stimulates insulin release and is associated with

blood pressure control. (Khardori, 2024).

CLINICAL SIGNS AND SYMPTOMS

Figure 3: Summary of the pathological effects T2DM has on different organs
and systems throughout the body, some of which directly contribute to
dyslipidaemia/hyperglycaemia and subsequent clinical symptoms:

Reference: Reid, Bain and Kanamarlapudi, 2021, p. 20, Figure 7.

Clinical signs and symptoms of T2DM can vary widely and may go unnoticed for
many years, particularly in the early stages of disease. (American Diabetes
Association, 2024).

T2DM can be asymptomatic, but common symptoms are:

 Hyperglycaemia (glucose blood levels rise due to IR and insulin deficit)

 Glucosuria (glucose spills in the urine)
 Polyuria (due to glucose in urine excreting osmotic pressure in the filtrate,
resulting in large urine volume and loss of fluid and electrolytes (Na+ and K+)
from the body tissues leading to dehydration)
 Polydipsia (dehydration causes thirst)
 Polyphagia (lack of nutrients entering cells stimulates appetite)
 Obesity, particularly central (excessive hypertrophy of adipocytes leading to
IR)
 Extreme fatigue (inability to utilise glucose)
 Blurry vision (high blood glucose damages the eye retina) and subconjunctival
haemorrhage
 Cuts/bruises that are slow to heal
 Tingling pain or numbness in the hands/feet (peripheral neuropathy caused by
high glucose damaging nerves)
  Acanthosis nigricans (brown, velvety patches of the epidermis as
keratinocytes replicate faster in the presence of high glucose)
 Candidiasis (Candida thrives in high glucose environments)
 Erectile dysfunction (poor glucose management can damage blood vessels
and nerves)
 Muscle atrophy (IR reduces myocyte protein synthesis)
 Ulcers (poor circulation from blood vessels damage and reduced sensation
from trauma)
 Deep tendon reflex loss (high glucose levels cause damage to the peripheral
nerves)
 As the disease progresses, signs and symptoms of micro and macro
complications (further discussed in detail under the prognosis/complications
heading).
(References: Wales Centre for Pharmacy Postgraduate Education, 2017; Hubert and
VanMeter, 2018; Chouhan et al., 2019; Galicia-Garcia et al., 2020; Reid, Bain and
Kanamarlapudi, 2021; American Diabetes Association, 2024; Khardori, 2024; NICE,
2024).

Figure 4: Acanthosis nigricans

Reference: College of Naturopathic Medicine [CNM], 2023, p.74.

Red Flags that need referral:

  Recurring episodes of hypoglycaemia (sweating, palpitations, tremor, hunger,
confusion, drowsiness). An adverse effect of insulin treatment, with blood
levels of glucose less than 3.5mmol/L.
 Signs of diabetic ketoacidosis (fruity breath, blurred vision, polyuria,
confusion, feeling tired and sleepy).
 Any signs of haematuria, dysuria or urinary urgency.
 Any symptoms of pancreatitis (abdominal pain, nausea and vomiting).
 Ulceration or degradation of foot tissue, even if it appears minor. There is a
risk of amputation due to reduced lower extremity blood flow.
 Hyperosmolar hyperglycaemic state. A blood glucose level of 30mmol/L for
several days with accompanying symptoms: disorientation, confusion,
drowsiness, polyuria, polydipsia. These present without signs of ketosis.
 Acute kidney injury (a sudden decline in renal excretory function over hours or
days).
(References: Wales Centre for Pharmacy Postgraduate Education, 2017; Khardori,
2024; NICE, 2024).

DIFFERENTIAL DIAGNOSIS

Table 1: Differential diagnosis of T2DM

Medical Similarities Differences

Pathology
Type 1 Diabetes Hyperglycaemia and Autoimmune condition, the insulin
(T1DM) associated signs and deficit results from pancreatic -
symptoms. cells destruction, usually
diagnosed in adolescence. Rapid
appearance of symptoms, always
treatment with insulin.
Drug-induced Insufficient insulin Absence of other risk factors.
Diabetes secretion and/or Introduction of medicines such as
production. beta-blockers, calcium-channel
blockers, protease inhibitors and
oral contraceptives with high doses
of oestrogen.
Gestational Insulin resistance. Develops during pregnancy and
Diabetes Insufficient insulin disappears after delivery of the
secretion. child. 5-10% of women with
gestational diabetes develop
 T2DM in the future.
Diabetes Polydipsia, polyuria. Unexplained weight loss. No
Insipidus hyperglycaemia. Not related to
blood sugar, but to insensitivity of
the kidneys to ADH (antidiuretic
hormone).
Polycystic Ovary Acanthosis nigricans, IR, Only occurs in females. Often
Syndrome obesity. Hyperinsulinemia. exhibits hyperandrogenism with
(PCOS) Inheritable genetic links associated symptoms such as
st
(increased risk with 1 hirsutism and acne vulgaris.
degree relatives). PCOS and T2DM could both be
present in a patient.
Decreased blood glucose Unintentional weight loss, agitation
Hyperthyroidism control, increased and nervousness, hyperactivity,
appetite, polyurea, fatigue. increased sweating.
(References: Hubert and VanMeter, 2018; College of Naturopathic
Medicine [CNM], 2023; NICE, 2024).

INVESTIGATIONS

Blood tests for diagnosis of T2DM are:

 Haemoglobin A1c (HbA1c)  48 mmol/mol (6.5%): average blood glucose

level over the preceding 2-3 months.
 Fasting Blood Sugar Test (FBST)- fasting plasma glucose level 7mmol/L,
(plasma glucose after an overnight fast of at least 8 hours).
 Random Blood Sugar Test (RBS)- random plasma glucose 11mmol/L (no
fasting, direct plasma glucose test), in the presence of symptoms and/or signs
of diabetes.
 Oral Glucose Tolerance Test (OGTT)- plasma glucose 11mmol/L (plasma
glucose levels are checked at 2 hours following ingestion of glucose-
containing liquid, and results compared to an overnight fasting blood test).

(References: LabTestsOnline, 2021; CDC, 2023; ADA, 2024; NICE, 2024).

Table 2: Comparisons between diabetes, prediabetes and normal blood
glucose:
Result HbA1c FBST OGTT RBS
 7 mmol/L or more
48 mmol/mol 11mmol/L or more 11mmol/L or more
Diabetes (126 mg/dL or
(6.5%) or above (200 mg/dL or more) (200 mg/dL or more)
more)

42-47 mmol/mol 6.1-6.9 mmol/L 7.8-11.0 mmol/L

Prediabetes N/A
(6.0 – 6.4%) (100-125 mg/dl) (140 – 199 mg/dL)

Below 42 mmol/mol Below 6.1 mmol/L Below 7.8 mmol/L Below 11.1 mmol/L
Normal
(Below 6.0%) (Below 100 mg/dL) (Below 140 mg/dL) (Below 200mg/dL)

(References: Sherwood, 2018; NICE, 2024).

Many patients with T2DM are asymptomatic and complications may develop way
before the diagnosis of T2DM. ADA, (2024) recommends testing in asymptomatic
adults who are overweight [BMI ≥25 kg/m2] and have one or more of the following
risk factors, including:

 First-degree relative with diabetes, physically inactive

 Hypertension- BP >140/90 mm Hg
 HDL cholesterol <35 mg/dL or triglyceride level >250mg/dL
 Polycystic ovary disease. (Khardori, 2024).

HbA1C test should not be used for children under 18, pregnant women and
individuals with disorders in red blood cell turnover. (NICE, 2024).

Other tests:

 Blood pressure.
 Glucose finger prick or continuous glucose meter (monitor blood glucose).
 Serum Creatinine (to calculate eGFR). Albumin: Creatinine Ratio (ACR),
Creatinine Clearance, Microalbuminuria (monitor kidney function).
 Triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol (monitor
lipids).
 Suspected ketoacidosis: urine and/or blood ketone tests.
 HbA1C for diagnosed gestational diabetes re-tested 6-13 weeks post-delivery.
 Digital retinal screening every 1 to 2 years (for diabetic retinopathy).
 Liver monitoring (increased risk no non-alcoholic fatty liver disease (about
50% of diabetics) and other liver diseases): Liver function tests (LFTs) such
as ALT and AST, Imaging (CT, ultrasound or MRI).
 C-Peptide levels (indicates how much insulin the pancreas is making).
(References: Giacomo, 2014; Zoppini, 2014; EASL, EASD and EASO, 2016;
Pizzorno, Murray and Joiner-Bey, 2016; LabTestsOnline, 2021; ADA, 2024; Diabetes
UK, 2024; NICE, 2024).

ORTHODOX MEDICAL TREATMENT

Currently there is no cure for T2DM, but remission is possible. Remission is when
HbA1c remains bellow 48mmol/mol (6.5%) for at least three months, without the
need for glucose lowering medications. (Diabetes UK, 2024).

NICE guideline [NG28] outlines recommendations on individualised care, patient

education, dietary advice and bariatric surgery, antiplatelet therapy, blood glucose
control and managing complications. (NICE, 2022).

Blood glucose should be kept at or below the target of 48mmol/mol (6.5%) HbA1c to
minimise the risk of long-term vascular complications. (NICE, 2022).

Treatment initially includes a single antidiabetic drug alongside lifestyle advice.

Metformin being the first-line drug treatment. If necessary, intensification of the
treatment is initiated until desired control of Hb1Ac is achieved. (NICE, 2024).

Lifestyle advice on:

 Diet: Importance of healthy, balanced diet with high-fibre, low glycaemic index
foods, low-fat dairy products and oily fish. Reduce intake of alcohol, foods
containing high saturated and trans-fatty acids, high sugar drinks and reduce
salt intake. Weight-loss target: 5-10%. (NICE, 2024).
 Exercise: Regular exercise and physical activity: aerobic exercise
150mins/week (moderate to vigorous), resistance exercise 2-3 times/week
and flexibility and balance training 2-3 times/week. (Kirwan, Sacks and
Nieuwoudt, 2017).
 Smoking cessation, alcohol intake (14 units/week), periodontitis. (NICE,
2024).
 Oral drugs often fail in hailing progression and patients eventually require insulin
replacement therapy. (Khardori, 2024).

Statins, anti-hypertensives and/or low dose aspirin to prevent complications. (CNM,

2023).

Table 3: Drug treatment options for T2DM:

Class Medicine Mode of Side-effects Cautions / Contra-

action Toxicities indications
Biguanide Metformin Inhibit Diarrhoea, Liver failure, Acute
gluconeogen abdominal pain, chronic kidney metabolic
esis in the nausea, disease acidosis, at
liver and vomiting, risk of lactic
increase the appetite acidosis
utilisation of decreased,
glucose by vitamin B12
the peripheral deficiency, lactic
tissue acidosis
Sulfonylureas Glibenclamide Stimulate ß- Abdominal pain, Weight gain, Ketoacidosis,
Gliclazide cells in diarrhoea, drug- elderly, G6PD acute
Glimepiride pancreas to induced deficiency, porphyria,
Glipizide produce hypoglycaemia, cardiovascular severe hepatic
Tolbutamide insulin nausea, hepatic comorbidities, impairment,
disorders, blood allergy, allergic avoid in
disorders dermatitis, renal pregnancy
impairment

Meglitinides Nateglinide Stimulate Abdominal pain, Liver failure, Ketoacidosis,

Repaglinide insulin diarrhoea, acute coronary avoid in
secretion by hypoglycaemia, syndrome pregnancy and
closing nausea and breast feeding
sensitive K+ vomiting
channels in
ß-cell
membranes
Thiazolidinedione Pioglitazone Reduces Bone fracture, Heart failure, Diabetic
peripheral increased risk of bladder cancer, ketoacidosis,
insulin infection, weight liver history of heart
resistance increased, dysfunction, risk failure, bladder
numbness, factors for bone cancer,
insomnia, visual fracture macroscopic
 impairment, haematuria,
hepatic elderly, avoid
impairment in pregnancy
and breast-
feeding
Dipeptidylpeptida Alogliptin Inhibit DPP4, Abdominal pain, Hepatic and Moderate and
se-4 inhibitors Linagliptin enzyme to GORD, renal severe heart
(gliptins) Sitagliptin increase headache, risk impairment, failure, hepatic
Saxagliptin insulin of upper history of impairment,
Vildagliptin secretion and respiratory tract pancreatitis, ketoacidosis
lower infections, skin heart failure, (not for
glucagon reactions, elderly linagliptin and
secretion hypoglycaemia, saxagliptin)
myalgia, joint
pain
SGLT2 inhibitors Canagliflozin Reversibly Hypoglycaemia, Diabetic Diabetic
Dapagliflozin inhibit renal balanoposthitis, ketoacidosis, ketoacidosis,
Empagliflozin reabsorption constipation, increased risk of type 1
Ertugliflozin of glucose in dyslipidaemia, lower limb diabetes
the proximal increased risk of amputations mellitus
convoluted infection, thirst, (mainly toes), (increased risk
tubule and nausea, urinary Fournier’s of
increase disorders, gangrene, renal ketoacidosis),
urinary urosepsis, failure, elderly, moderate and
glucose dehydration, risk of volume severe renal
excretion, hypotension, depletion, impairment,
has a proven Fournier’s elevated severe hepatic
cardio- gangrene, high haematocrit, impairment,
vascular cholesterol hypotension active foot
benefit disease
Glucagon-like Dulaglutide Bind to and Hypoglycaemia, GI motility Diabetic
peptide-1 Exenatide activate weight loss, disorders, ketoacidosis,
receptor agonists Liraglutide GLP-1 appetite diabetic avoid during
(GLP-1) Lixisenatide receptor to decreased, retinopathy, pregnancy and
Semaglutide increase cholelithiasis, history of breast feeding
insulin gastrointestinal pancreatitis,
secretion, disorders, pancreatic
suppress nausea,burping, cancer, severe
glucagon vomiting, congestive heart
secretion and diarrhoea, failure
slow gastric fatigue, taste
emptying altered,
alopecia
Insulin Short-acting Insulin Main: Hypoglycaemia Close
insulins, replacement hypoglycaemia, monitoring
intermediate hunger, anxiety, during
and long- palpitations, pregnancy and
acting insulins sweating, breastfeeding
headache,
drowsiness,
 impaired vision,
confusion,
oedema, weight
gain

(Reference: NICE, 2024).

NATURAL MEDICINE

Herbs can support conventional medicines, helping to manage diabetes symptoms.

Several herbs have been studied for their potential use in T2DM management.

Also, it is important to note that some herbs can potentially interact with orthodox
medicines and a physician and/or qualified herbalist should be consulted prior to
starting supplementation.

Here are some herbs commonly used and studied for their potential effects on
T2DM:

Gymnema sylvestre

 A plant with potent antidiabetic properties native to tropical forests in India and
is used in both Aryvedic and Western medicines.
 It possesses anti-oxidant, anti-inflammatory, anti-helminthic, hypolipidemic
and anti-obesity activities.
 Active ingredient: a group of acids known as gymnemic acids.
 Gymnemic acids may stimulate insulin secretion and inhibit glucose
absorption in the intestine (thus reducing postprandial blood glucose levels).
 Gymnema promotes regeneration of pancreatic ß-cells, improves insulin
sensitivity in insulin-resistant tissues, improves glycaemic control in T2DM,
reducing the need for hypoglycaemic drugs.
 Applied to the tongue, gymnemic acid temporarily blocks sensation of
sweetness, which may reduce cravings for sugary foods.

(References: Rios, Francini and Schinella, 2015; Pizzorno, Murray and Joiner-Bey,
2016; Venkatakrishnan, Chiu, and Wang, 2019).
Ginseng species

 Panax ginseng (Chinese or Korean ginseng) and Panax quinquefolius

(American ginseng) have been most studied for their effect on T2DM.
 Preparations use the rhizome (root) and the main active components are
triterpenoid saponin glycosides (ginsenosides and panaxosides).
 Mechanisms of action include: decreased rate of carbohydrate absorption into
the portal hepatic circulation, increased glucose transport and glucose uptake
and glycogen synthesis, increased glycogen storage, inhibit gluconeogenesis
and increase production of insulin.
 Positively regulate various insulin signalling pathways.

(References: Rios, Francini and Schinella, 2015; Venkatakrishnan, Chiu, and Wang,
2019).

Momordica charantia

 Known as bitter melon, bitter gourd, balsam pear.

 Fruits, seeds are leaves are widely used and preparations range from
injectable extracts to fruit juice and fried melon bits.
 Active components are charantin (hypoglycaemic constituent composed of
mixed steroids more potent than the drug tolbutamide), vicin and polypeptide-
P (insulin-like polypeptide similar to bovine insulin).
 Mechanisms of action include increased insulin secretion, tissue glucose
uptake, liver muscle glycogen synthesis, glucose oxidation and reduced
gluconeogenesis, enhanced insulin sensitivity.

(References: Yeh, et al., 2003; Rios, Francini and Schinella, 2015; Venkatakrishnan,
Chiu, and Wang, 2019).

Ginkgo biloba

 According to Pizzorno, Murray and Joiner-Bey (2016), it is a best choice for

people over 50. Flavonoid- rich extract protects brain and vascular lining. Very
 important in improving blood flow to the extremities, neuropathy and foot
ulcers.
 Exerts hypoglycaemic effects by increased peripheral glucose uptake,
improve insulin sensitivity, protect ß-cells from apoptosis and enhance insulin
secretion.
 Renoprotective and nephroprotective action in diabetic patients.
 Ginkgo biloba shows anti-oxidant, anti-inflammatory, hypolipidemic, anti-
obesity and anti-tumour activities. (Venkatakrishnan, Chiu, and Wang, 2019).

Trigonella foenum-graecum

 Fenugreek seeds.
 Bioactive components are special insoluble and soluble fibre, alkaloid
trigonelline, 4-hydroxyisoleucine.
 Modes of action: improve insulin sensitivity, delay gastric emptying, inhibit
hepatic gluconeogenesis and protect ß-cells from apoptosis, enhancement of
glucose uptake in peripheral tissues.
 Antioxidant and anti-inflammatory effects may help reduce oxidative stress
and inflammation associated with T2DM.

(References: Rios, Francini and Schinella, 2015; Venkatakrishnan, Chiu, and Wang,
2019).

Allium sativum (garlic)

 Contains a broad spectrum of active ingredients, such as sulphur containing

compounds: allyl propyl disulfide, allicin and many more.
 Antioxidant, anti-inflammatory, anti-obesity, hypolipidemic, blood sugar-
lowering action, anti-atherosclerotic, anti-coagulant, making it very beneficial
for diabetic patients.
 Lowers glucose by competing with insulin for insulin-inactivating sites in the
liver, hence increasing free insulin.
 Inhibits glucose absorption and transportation, inhibits hepatic
gluconeogenesis as well as increasing glucose utilisation.
 Wang et al. (2017) concluded that supplementation with garlic for 12-24
weeks would positively contribute to blood glucose control and total
 cholesterol and high/low density lipoprotein regulation in diabetic patients and
is used in the management of T2DM and its complications.

(References: Wang et al. 2017; Venkatakrishnan, Chiu, and Wang, 2019).

PROGNOSIS/COMPLICATIONS

On average, life expectancy in T2DM cases is reduced by 10 years, and in England

diabetes accounts for 15-16% of all deaths. (NICE, 2024).
In 2019, it was the 9th leading cause of death globally. (WHO, 2024).

The prognosis for T2DM varies depending on factors such as glycaemic control,
presence of complications, comorbidities and adherence to treatment and lifestyle
modifications. (WHO, 2023).

Complications associated with T2DM are: macrovascular, microvascular, metabolic

and psychological. T2DM can also be linked to reduced quality of life, an increased
risk of infection, reduced life expectancy and dementia. (NICE, 2024).

Macrovascular
 Atherosclerotic cardiovascular disease, including myocardial infarction.
Myocardial infarctions are 2.5 times more prevalent and CVD is the leading
cause of death in those diagnosed with T2DM.
 cerebrovascular disease (stroke and transient ischaemic attack) with two-fold
increased risk of stroke within first 5 years of T2DM diagnosis.
 peripheral arterial disease (commonly observed as diabetic foot).
(References: WHO, 2023; NICE, 2024).

Microvascular
 Diabetic nephropathy:
 The hyperglycaemic-induced glomerular disease results in albuminuria
and leads to hypertension.
 1 in 5 people with diabetes will need treatment for diabetic nephropathy
and 10-20% die of kidney failure. (WHO, 2011; Diabetes UK, 2024).

 Retinopathy:
 Damaged eye blood vessels lead to cotton wool spots and haemorrhages
as the disease progresses. (BMJ Best Practice, 2024).
  A leading cause of preventable sight-loss in the UK and 7% of newly
registered blind in the UK have lost their sight due to diabetes. (NICE,
2024).

Figure 5: Proliferative retinopathy with venous bleeding, cotton wool

spots and some hard exudates:

(Reference: Watkins, 2003).

 Peripheral neuropathy:
 Estimated to affect about 50% of patients. (WHO, 2011). Presents as
numbness, burning or shooting pains, tingling that can become persistent.
 This can lead to diabetic foot problems ultimately resulting in loss of
sensation which paired with trauma can lead to loss of limb and life-
threatening situations, such as sepsis. (NICE, 2024).

 Autonomic neuropathy causing:

 Postural hypotension, gastroparesis, unexplained diarrhoea, sexual
dysfunction, including erectile dysfunction, etc. (Diabetes UK, 2024; NICE,
2024).

Metabolic
 Dyslipidaemia (risk factor for CVD).
 Diabetic ketoacidosis (DKA) – life-threatening emergency characterised by
triad of hyperglycaemia, metabolic acidosis and ketonaemia. (NICE, 2024).
 Hyperosmolar hyperglycaemic state (HHS)- life-threatening emergency.
Severe hyperglycaemia and dehydration. (Diabetes UK, 2024; NICE, 2024).

Psychological
 Anxiety and depression- T2DM impacts negatively quality of life doubling the
prevalence of depression compared to general population. (NICE, 2024).
  Cognitive decline. (Khardori, 2024).

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