Diabetes mellitus

From Ganfyd

Type 1 diabetes mellitus - treat with insulin Type 2 diabetes mellitus - metformin has best evidence base if diet insufficient Monogenetic diabetes -can specifically require sulphonylureas so know when to suspect

Diabetes mellitus is a group of diseases characterised by hyperglycaemia. This can arise either from lack of secretion of insulin from the β islets of the pancreas or due to resistance to the action of insulin. They are commonly referred to as Type 1 and Type 2. A further type of diabetes mellitus is called Secondary Diabetes.

Strict control of blood sugar is an important part of the management. Poor control has been shown to increase the chances of developing heart, kidney and eye problems. In recent years it has become clear that control of blood pressure is also critical, indeed the benefits to be had from control of blood pressure may be similar in magnitude to those from glucostasis. Diabetes, however, is a progressive condition.

In addition to diabetes mellitus we now recognise impaired glucose tolerance and IFG impaired fasting glucose; DM, IGT and IFG are manifestations of defects of insulin action e.g.insulin resistance, insulin production beta-cell failure or both.

Secondary Diabetes

due to

• Cushing's syndrome
  • Cushing's disease
  • Oral steroids
• Infection

Risk factors for complications of Type 1 diabetes Poor glycaemic control Smoking Sedentary lifestyle Hypertension Hyperlipidaemia Early onset and long duration Genetics Obesity

Type 1

• Seen in younger individuals - usually under 40 years of age
• North european predominance
• Human lymphocyte antigen DR3/DR4 very common
• Destruction of the islets of Langerhans - insulitis
• Possibly viral triggered autoimmune disease
• May be other autoimmune diseases - thyroid failure, ovarian failure, Addison's disease
• Antibodies found
• Seems to present more when viral illnesses more prevalent
• Suggested viruses are coxsackie B
• Prone to ketoacidosis
• Presentation is polyuria, polydipsia, weight loss, balanitis and sometimes with diabetic ketoacidosis
• All patients will require Insulin as well as dietary measures

Type 2

• Older individuals but now beginning to present in younger patients due to dietary excess
• Presentation is polyuria, polydipsia, polyphagia, and are usually overweight.
• Diabetic ketoacidosis does not occur
• All races especially Pima indians, polynesians, African, Asians.
• Insulin resistance i.e. Insulin is present but for various reasons its effectiveness is diminished
• Patients are treated by weight reduction, exercises, diet and medications. Some cases may require Insulin.
• Insulin is not vital but can improve control and reduce complications long term

Ketosis prone diabetes

Usually all the phenotypic features of type 2 diabetes but prone to ketoacidosis at times of severe stress or infection; there is reversible glucose toxicity at the beta cell. Seems to be relatively confined to black patients.

Monogenic Diabetes

A single gene failure could knock out the ability to produce functional insulin, or the control mechanisms for its secretion. One class of monogenic diabetes is MODY - maturity onset diabetes of the young - which differs from type 2 diabetes in that patients may appears to be doing relatively well, and by the considerable response to sulphonylurea drugs of some variants. Genetic testing in the UK is centred on Exeter. See genetics of diabetes.

Aetiology

Type 1 diabetes is caused by hereditary and environmental factors. A hypothesis is that there is a window of time for an infection with a coxsackie virus to trigger an auto-immune process destroying the insulin producing cells of the islets.

The genetics of diabetes is not fully understood.

Exclusion, screening and case finding

In the UK there is a de facto screening program with random urine testing on joining general practice lists. Previously there was a general policy of testing urine on attendance at hospital, but this is less common now. Severe diabetes, but not early diabetes can be excluded with reasonable certainty by a urine test, which is easy, cheap and generally acceptable. Random capillary glucose, fasting capillary glucose, fasting venous blood glucose and a 2 hour glucose challenge exclude diabetes with increasing reliability, cost and pain.

Much diabetes is discovered by case-finding - a somewhat targetted testing of people with conditions suggesting diabetes may have been present for some time.

Clinical

Diagnosis

• Onset is usually insidious with malaise and polydipsia
• May progress rapidly to diabetic ketoacidosis in type 1 diabetes

Investigations

Blood tests

The primary test for diabetes is a measurement of sugar level. Urine sugar levels can rule in diabetes, but not wholly rule it out in its early stages. They are simple and cheap.

In an asymptomatic patient any diagnostic test for diabetes must be repeated on a separate occasion. In a symptomatic patient, or a patient with specific complications of diabetes mellitus, one diagnostic test will suffice.

• Diagnostic
  • Fasting plasma glucose: >6.9 mmol/L
  • Random plasma glusose:>11 mmol/L
  • 2 hours after a 75 g glucose load >11 mmol/L
• Renal profile including bicarbonate and chloride
• Thyroid function test: TSH, T4 +/- T3
• LFT
• Lipid profile
• HbA1c (not used for diagnosis, only for follow up).

C-peptide may be measured as a proxy for endogenous insulin secretion. Antibodies to islet cells may indicate whether diabetes is early type 1 or is type 2, in the minority of cases where this is not clinically evident.

Radiology

Treatment

Medical

• Lifestyle change: This is the first and most crucial part of management of diabetes;
  • Diet. The most significant diet modification in type two diabetes is a reduction in energy content sufficient to cause a reduction in body weight (except in the rare type two diabetic who is not fat). Diet modifications include: sugar free, foods with high glycaemic index, fruit and vegetables,low fat and salt diet.
  • Weight reduction
  • Regular exercise. Aerobic and resistance training improves glycaemic control in type 2 diabetes^[1]
• Management of hypertension to a lower target than non-diabetics
• Management of hypercholesterolaemia - or indeed normal levels of cholesterol^[2].

Hypoglycaemic agents

• Metformin
• Sulphonylureas
• Prandial glucose modulators
• Glitazones
• Acarbose
• Insulin

Surgical

Transplantation of the pancreas tends to cure Type 1 Diabetes, but is hazardous enough to only be done when a kidney is also being transplanted.

Transplantation of islet cells is effective to a degree and will be offered on a small scale in the UK from April 2008^[3].

In patients undergoing bariatric surgery, exclusion of the duodenum appears to improve glycaemic control after several weeks, which is faster than would be expected from weight loss alone. This phenomenon has been reproduced in a rat model^[4]. A case series of 11 patients shows that this phenomenon may be potentially exploited in treating diabetes in non-obese patients through surgical partial duodenal bypass (duodeno-jejunal bypass).^[5]

Progression and complications

Diabetic maculopathy

Diabetic nephropathy

Atherosclerosis

Curing Diabetes

We should be able to cure Type 1 diabetes.

References