Overview Diabetes Mellitus type II is a progressive disorder defined by deficits in insulin secretion and action (insulin resistance). 1 in 12 people have diabetes (50% do not know they have it). Diabetes type II accounts for over 90% of all diabetes cases. The remaining 10% include type I diabetes. People with type II diabetes are often asymptomatic initially, and may not be recognised for many years. Type II is not usually associated with DKA and insulin is not essential for survival but is often required to achieve adequate glycemic control.

The pancreas sits in the upper abdomen behind the stomach. The pancreas consists of the following parts:

• Head
• Neck
• Body
• Tail

The head is encircled by duodenum and tail in contact with spleen. The pancreas has a poorly developed capsule & therefore adjacent structures (common bile duct, duodenum, splenic vein, transverse colon) are commonly involved in inflammatory process. It is an exocrine and endocrine organ.

Blood Supply

• Pancreatic branches of the splenic artery
• Superior pancreaticoduodenal artery
• Inferior pancreaticoduodenal artery

Venous drainage

• Drains with the splenic vein → Superior Mesenteric → Portal vein

Nerve invervation

• Parasympathetic → Vagus nerve → Stimulates pancreatic juice secretion
• Sympathetic

Lymphatic drainage

• Head and Neck → Pancreticoduodenal nodes →
• Body and Tail → Pancreaticosplenic nodes →

Embryology

• Fusion of the ventral and doral outpounchings of foregut

Exocrine glands bundle up to form the pancreatic acinar which secrete digestive enzymes into the pancreatic duct which makes its way to the ampulla of vater and into the duodenum. The pancreatic duct joins with the common cystic duct. There is the main pancreatic duct and an accessory pancreatic duct which does not join with the common cystic duct so when obstruction occurs due to gallstones, the pancreas is still able to secrete its enzymes into the duodenum. Pancreatic enzymes include:

• Beta-amylase
• Protease
• Lipase

The endocrine cells make up the islets of Langerhan in the pancreas. The Islet of Langerhan make up 2% of the pancreas. There are many endocrine cells:

• Alpha cells → Glucagon
• Beta cells → Insulin
• Delta cells → Somatostatin

Mechanism of Insulin release and function of insulin on target organs

The Beta cells produce insulin. The beta cells make up the majority of endocrine cells in the pancreas. Beta cells are stimulated when blood glucose is high. Once insulin is secreted it targets many organs especially the liver to promote glucose storage as glycogen and lipids.

Normal physiology of what happens after you eat. Insulin plays a major role in the bodies response to feeding. Insulin promotes storage of nutrients. Insulin dysfunction results in elevated glucose levels and distributes homeostasis.

Diabetes in General

• Asymptomatic period
• Infections
• Fatigue
• Blurred vision
• 4Ps
  • Paresthesia
  • Polydipsia
  • Polyuria
  • Polyphagia

Diabetic Complications (advanced disease)

Diabetic Retinopathy

• Poor vision

Diabetic Neuropathy

• Peripheral neuropathy
  • pain
  • loss of sensation
  • dysaesthesia
  • weakness
• Autonomic neuropathy
  • resting tachycardia
  • orthostatic hypotension
  • erectile dysfunction
  • constipation

Diabetic Nephropathy

• Oedema
• Anaemia
• Hypertension
• Uremia

More info on the Long-Term Complications of Diabetes

• HbA1c
• Fasting plasma glucose
• Random plasma glucose
• 2-hours post-load glucose
• Lipid profile
• Urine ketones
• Urine albumin

Diabetes case detection 

• Its important to screen for people with risk factors for diabetes. This can be done using venous plasma glucose levels
• In all asymptomatic people whose initial result suggests a diagnosis of diabetes, a confirmatory test must be performed on a separate day.

Diagnosis (7/11 rule)

• Fasting Blood Glucose ≥7.0 mmol/L (on two separate occasions)
• 2 hour postprandial ≥11.0 mmol/L on OGTT- Oral Glucose Tolerance Test (on two separate occasions)
• HbA1c ≥6.5% (48 mmol/mol) (on two separate occasions)

*There is no definitive diagnostic criteria  for Diabetes. The criteria varies between countries

Differential Diagnosis for Diabetes Type II

• Diabetes Mellitus type 1
• LADA (latent autoimmune diabetes of the adult)
• Gestational diabetes
• Diseases of the exocrine pancreas (cystic fibrosis, chronic pancreatitis, haemochromotosis)
• Cushing disease
• Glucocorticoid use
• Genetic syndromes (Down's syndrome, Turners syndrome)

Differential Diagnosis for Diabetic Complications

Differential Diagnosis for Diabetic Retinopathy

• Hypertension
• Retinal vessel occlusion

Differential Diagnosis for Diabetic Neuropathy

• Uraemia
• Vitamin B12 Deficiency
• Hypothyroidism
• Wernicke and Korsakoff
• Cauda equina problems
• Guillian-Barre syndrome
• Charcot-Marie-Tooth disease

Differential Diagnosis for Diabetic Nephropathy

• Glomerulonephritis
• Renal artery stenosis
• Renal tract obstruction
• Multiple Myeloma

• Genetic predisposition
• Physical inactivity and being overweight contributes to insulin resistance.

Management priorities for diabetes are

• To relieve symptoms of hyperglycemia
• To avoid acute complications of hyperglycemia, such as diabetic ketoacidosis and hyperosmolar nonketotic coma
• To avoid hypoglycemia
• To reduce the risk of long-term end-organ complications

General Management

• Education in self monitoring and emergency
• Monitor HbA1c
• Healthy eating plan
• Exercise program
• Reduction in cardiovascular risk factors (smoking, blood pressure, lipids)
• Pharmacological therapy
• Use of insulin if required
• Screening for complications (more info below)

Screening for Diabetic Complications

• Diabetic Retinopathy
  • Fundoscopy
• Diabetic Neuropathy
  • Neuro examination
  • Foot check
• Diabetic Nephropathy
  • Urinalysis for proteinuria
  • Urinary albumin/creatinine ratio
  • EUC
  • GFR

Microvascular Complications

• Diabetic Retinopathy
• Diabetic Neuropathy
  • Peripheral neuropathy
  • Autonomic neuropathy
• Diabetic Nephropathy

Macrovascular Complications

• Coronary Heart Disease
• Cerebrovascular Disease
• Peripheral Vascular Disease

More info on the Long-term Complications of Diabetes

Other complications

• Hypoglycaemia - due to patients treated with insulin or insulin secretagogues

• Alcohol associated hypoglycaemia - alcohol impairs the body's ability to provide glucose and restore low glucose concentrations towards normal.
• Diabetic Ketoacidosis - occurs more often in Diabetes type I and is characterised by hyperglycamiea, polyuria, polydipsia, hyperventilation and dehydration (can occur with type II)
• Hyperosmolar Hyperglycemia - Occurs primarily in type II diabetes and is characterised by marked hyperglyceamic and dehydration without ketoacidosis. It may present as coma in severe cases and can be precipitated by sepsis. Venous thromboemoblism is a common complication of hyperosmolar states and heparin should be used prophylactically.
• Lactic Acidosis - occurs especially if patients with diabetes have renal impairment or they are in a hypoxic state. Most commonly, lactic acidosis occurs in the setting of tissue hypoxia secondary to shock and hypotension. Lactic acidosis can also be caused by Metformin
• Diabetic cardiomyopathy
• Diabetic musculoskeletal complications - cheirarthropathy, carpal tunnel syndrome and frozen shoulder
• Peridontal disease

Prognosis

• Adults with Type II diabetes are twice as likely to die from stroke or MI
• Diabetes is the most common cause of Chronic Kidney Disease worldwide

UpToDate
BestPractice
Endocrinology Therapeutic Guidelines 2009
Oxford handbook of clinical medicine