Diabetes MellitusMedical Management and Latest Developments

Dr Ahmad Abou-Saleh

What is Diabetes Mellitus?

A disease characterised by a state of chronic elevation of blood glucose levels due to:

- The body’s inability to produce insulin (insulin deficiency)

And/Or

- The body’s inability to respond to insulin (insulin resistance)

United Kingdom

• 6 – 8% of UK Population is Diabetic

• Approximately half a million undiagnosed Diabetics in the UK at any one time

• 5 Million Diabetics in UK by 2025

• 10% of NHS Budget is spent on Diabetes care (~£10 Billion)

Type 1 Diabetes Mellitus

• A disorder of the immune system where the body’s own ability to produce insulin is destroyed (nearly 100%)

• Immune system wrongly target

and destroy β-cells in the Pancreas

• This can only be managed by

immediately starting insulin therapy

Type 2 Diabetes Mellitus

• 95% of all Diabetics are Type 2

• Combination of insulin deficiency (though not as much as Type 1 Diabetes Mellitus) and insulin resistance

• Associated with Obesity, Hypertension and Hypercholesteraemia

• Managed by a combination of diet, oral medications and injectable therapies (e.g. insulin)

Diabetic Complications

Eye Disease

Kidney Disease

Heart Disease

Cerebrovascular Disease

Nerve Disease

Peripheral Vascular Disease

Foot Disease

Some of the potential outcomes of Diabetes!Cataracts

Glaucoma

Retinopathy

Blindness

End-Stage Renal Failure

Dialysis

Kidney Transplant

Heart Attack

Heart Failure

Arrhythmias

Mini-Stroke

Stroke

Sensory Ataxia

Painful Peripheral Neuropathy

Mononeuritis Multiplex

Lumbosacral Plexopathy

Muscle Infarction

Intermittent Claudication

Acute Ischaemia and Necrosis

Foot Ulceration

Toe Amputation

Major Limb Amputation

Diabetic Foot Disease

• Definition: Localised injury to the skin and/or underlying tissue (below the ankle) in a person with Diabetes

10% of all Diabetics will be diagnosed with a foot ulcer in their lifetime

50% will die within 5 years of developing a diabetic foot ulcer

70% will die within 5 years of having an amputation

• Diabetes is the most common cause of non-traumatic limb amputation

Risk Factors for Diabetic Foot Disease

• Neuropathy

• Peripheral ischaemia

• Swelling

• Skin breakdown

• Infection

• Deformity

• Callus

Treatment for Diabetes

• Type 1 Diabetes Mellitus

Multiple daily insulin injections

Diet and Exercise

• Type 2 Diabetes Mellitus

Diet, exercise and weight loss

Oral and/or injectable anti-diabetic medications (including insulin)

Treat Hypertension and Hypercholesteraemia

Aims of Treatment

• Prevent onset of complications

• Slow the progression or cause reversal of existing complications

• Prevent extremes of blood glucose levels (hyperglycaemia, hypoglycaemia)

• Manage other risk factors e.g. Hypertension, Hypercholesteraemia

NICE Guidance on Type 2 Diabetes Mellitus

Treatment for Diabetes – Oral Medication

• Biguanides – Metformin – Improve insulin sensitivity

• Sulphonylureas – Gliclazide – Enhance insulin secretion

• Thiazolidinediones – Pioglitazone – Improve insulin sensitivity

• DPP4-inhibitors – Sitagliptin – Enhance effect of beneficial gut hormones

• GLP-1 Analogues – Liraglutide (injection) – Synthetic beneficial gut hormone

• SGLT2 inhibitors – Empagliflozin – Enhance excretion of glucose into urine

Diabetes and Insulinhow far have we come?

Glucose lowering agentstypes of insulin available

• Mealtime insulins

• unmodified human

• soluble

• regular

• rapid-acting analogues

• Basal insulin

• NPH insulin

• protamine complex

• long-acting analogues

• Insulin mixes

• soluble + NPH

• rapid acting analogues + NPH

• Type 1 Diabetes Mellitus

• Fast-acting insulin with meals and 1- 2 basal insulin injections – optimal

• Twice daily mix insulin

• Type 2 Diabetes Mellitus

• Once – Twice daily basal insulin

• Twice daily mix insulin

• Fast-acting insulin with meals and 1- 2 basal insulin injections

Glucose lowering agentspossible insulin regimens

Monitoring Diabetes

• Daily self-monitoring with use of blood glucose meters

• Glycosylated Haemoglobin (HbA1c): Spot blood test providing information on average blood glucose over last 2 – 3 months

Updates in Type 2 Diabetes Mellitus

Personalised Care

New Glucose Lowering Agents

• GLP-1 Analogues (injection): Synthetic gut hormone which works to reduce weight as well as blood glucose

• SGLT2 inhibitors: Stimulates the kidney to allow more glucose to be removed in the urine – also helping to reduce weight alongside blood glucose

GLP-1 Analogue: Liraglutide injections

SGLT2 Inhibitor: Empagliflozin

SGLT2 Inhibitor: Canagliflozin

Diabetes reversal after <6 months low calorie diet

• Special formula diet (approximately 820 kcal/day)

• Nearly 50% had average blood glucose below the diabetic range (in “remission”) versus 4% through conventional measures

• Progressively greater odds of successful remission of Diabetes with a higher amount of weight loss

Updates in Type 1 Diabetes Mellitus

Peptide Vaccine for newly Diagnosed Type 1 Diabetes Mellitus

• Similar principles to vaccines for infections!

• Newly diagnosed diabetics given subcutaneous injections every 2 –4 weeks for 6 months

• Preserves insulin production and better diabetic control (and lower insulin doses) in treatment group

Closed-Loop System “Artificial Pancreas”

Benefits• Improved diabetic control (glucose

variability and average glucose values

• Reduced amount of time patients spent with low blood glucose values (hypoglycaemia)

• Automatic suspension of insulin delivery via pump when blood glucose drops too low

Glucose Monitoring now available on the NHS

Islet Cell Transplantation

Summary

Diabetes caused by insulin deficiency and/or resistance

Rising numbers UK and worldwide

Managed by lifestyle modification, oral and injectable therapies

Various developments – ongoing!