Diabetes Mellitus

Diabetes mellitus (DM) is a disease caused by deficiency or diminished effectiveness of endogenous insulin. It is characterised by hyperglycaemia, deranged metabolism and sequelae predominantly affecting the vasculature. The main types of diabetes mellitus are:

• Type 1 diabetes mellitus: results from the body's failure to produce sufficient insulin.
• Type 2 diabetes mellitus: results from resistance to the insulin, often initially with normal or increased levels of circulating insulin.
• Gestational diabetes: pregnant women who have never had diabetes before but who have high blood sugar (glucose) levels during pregnancy are said to have gestational diabetes. Gestational diabetes affects about 4% of all pregnant women. It may precede development of type 2 (or rarely type 1).
• Maturity onset diabetes of the young (MODY) includes several forms of diabetes with monogenetic defects of β-cell function (impaired insulin secretion); usually manifesting as mild hyperglycaemia at a young age, and usually inherited in an autosomal dominant manner.^1,2
• Secondary diabetes: accounts for only 1-2% of patients with diabetes mellitus. Causes include:
  • Pancreatic disease: cystic fibrosis, chronic pancreatitis, pancreatectomy, carcinoma of the pancreas
  • Endocrine: Cushing's syndrome, acromegaly, thyrotoxicosis, phaeochromocytoma, glucagonoma
  • Drug-induced: thiazide diuretics, corticosteroids, atypical antipsychotics, antiretroviral protease inhibitors
  • Congenital lipodystrophy
  • Acanthosis nigricans
  • Genetic: Wolfram syndrome (which is also referred to as DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy and deafness),³ Friedreich's ataxia, dystrophia myotonica, haemochromatosis, glycogen storage diseases

Some patients with type 2 diabetes require insulin so the old terms of insulin-dependent diabetes mellitus (IDDM) for type 1 diabetes and non insulin-dependent diabetes mellitus (NIDDM) for type 2 diabetes are inappropriate. Type 2 diabetes is increasingly diagnosed in children and adolescents and so the old term maturity-onset diabetes for type 2 diabetes is also inappropriate.

• Approximately 15% of diabetics; usually juvenile onset, but may occur at any age. It may be associated with other autoimmune diseases. It is characterised by insulin deficiency.
• Concordance is >30% in identical twins; 4 genes are thought to be important. One (6q) determines islet sensitivity to damage, e.g. from viruses or cross-reactivity from cow's milk-induced antibodies.
• Associated with HLA DR3 and DR4 and islet cell antibodies around the time of diagnosis. Patients always need insulin treatment and are prone to ketoacidosis.
• Risks of developing type 1 diabetes are broadly similar in all ethnic groups; however, environmental factors may also play a role.⁴
• The term 'type 1a diabetes' is being applied to the development of type 1 diabetes in adulthood. It is thought to result from a chronic autoimmune T cell-mediated islet cell destruction. Research may elucidate the underlying mechanisms, giving hope of prevention through identification and treatment of those at risk.⁵

• Approximately 85%. Usually older at presentation (usually >30 years of age) but increasingly diagnosed in children and adolescents.
• Type 2 diabetes is associated with excess body weight and physical inactivity.
• All racial groups are affected but increased prevalence in people of South Asian, African, African-Caribbean, Polynesian, Middle-Eastern and American-Indian ancestry.
• Caused by impaired insulin secretion and insulin resistance and has a gradual onset.
• Type 2 diabetics may eventually need insulin treatment.

• Over 5% of men and 4% of women in England have diagnosed diabetes.
• It has been estimated that 3.1% of men and 1.5% of women aged 35 and over have undiagnosed diabetes.
• The proportion of people with diabetes increases with age.
• The incidence of diabetes is increasing in all age groups. Type 1 diabetes is increasing in children (especially <5 years), and type 2 diabetes is increasing, particularly in black and minority ethnic groups.

Risk factors

• People of South Asian, African, African-Caribbean, Polynesian, Middle-Eastern and American-Indian descent are at greater risk of type 2 diabetes, compared with the white population.
• People who are obese, are inactive or have a family history are also at increased risk of type 2 diabetes.
• The metabolic syndrome is thought of as a precursor to type 2 diabetes. It is poorly defined and represents a heterogeneous collection of various propensities to diabetes. It has been suggested that lifestyle-intervention and treating metabolic manifestations of this pre-diabetic state can reduce the chance of progression to frank diabetes and the risk of complications.^7,8,9
• Genetic factors are complex and interact with environmental factors in a poorly understood fashion.^4,10
• Gestational diabetes and impaired glucose tolerance.¹¹

• Patients with all types of diabetes may present with polyuria, polydipsia, lethargy, boils, pruritus vulvae or with frequent, recurrent or prolonged infections.
• Patients with type 1 diabetes may also present with weight-loss, dehydration, ketonuria and hyperventilation. Presentation of type 1 diabetes tends to be acute with a short duration of symptoms.
• Presentation in patients with type 2 diabetes tends to be sub-acute with a longer duration of symptoms.
• Patients with diabetes may present with acute or chronic complications, as outlined in the section 'Complications' below.

The World Health Organisation (WHO) considers a patient to be diabetic if:¹²

• They have a fasting blood glucose of 7 mmol/l or higher.
• The 2-hour plasma glucose is 11.1 mmol/l or higher, as part of a standard or abbreviated oral glucose tolerance test (OGTT) - exact diagnostic criteria are discussed in the separate record Glucose Tolerance Tests.

• Assessment: see separate article Assessment of the Established Diabetic.
• Monitoring: see separate articles Glycosylated Haemoglobin, Glucose Monitoring, Self-Monitoring Blood Glucose in Diabetes Mellitus, Urine Glucose Monitoring in Diabetes Mellitus

The aims of treatment are the avoidance of complications, which include hypoglycaemia as well as the long-term consequences of hyperglycaemia. Strict plasma glucose control does reduce renal, neurological and retinal damage, although macrovascular disease is unaffected.^13,14,15 A balance is required for each patient between lower blood glucose readings and the risk of hypoglycaemia. Tight blood pressure control is as effective in reducing microvascular disease, but also reduces macrovascular disease, and mortality.^16,17 A global assessment of an individual's cardiovascular risk is essential.

• See separate articles: Standards and Aims of Diabetic Care, Managing Diabetes In General Practice, Management of Type 1 Diabetes, Management of Type 2 Diabetes.
  • Subsequent management of the new diabetic: see The Newly Diagnosed Diabetic.
  • Non-pharmacological treatment: see Diabetes Diet and Exercise, Diabetes Education and Self Management for Ongoing and Newly Diagnosed (DESMOND)
  • Oral medication: see Diabetes, Oral Hypoglycaemic Agents and Exanatide
  • Insulin: see Insulin Regimens, Dose Adjustment For Normal Eating and Exercise (DAFNE)
  • Specific circumstances: see Precautions with Diabetic Patients Undergoing Surgery, Diabetes and Intercurrent Illness and Diabetes in Pregnancy.
• Audit: see Diabetic Audit

• Acute:
  • See separate articles: Diabetic Ketoacidosis, Hyperosmolar Non-Ketotic Coma (HONK)
  • Complications of treatment: Emergency Management of Hypoglycaemia
• Chronic:
  • Cardiovascular disease: ischaemic heart disease, cerebrovascular disease, peripheral vascular disease
  • Renal: see Diabetic Nephropathy
  • Eye: see Diabetic Retinopathy and Diabetic Eye Problems
  • Neuropathy: see Diabetic Neuropathy, Autonomic Neuropathy, Neuropathic Pain and its Management
  • Foot problems: see Diabetic Foot, Leg Ulcers, Painful Foot
  • Frequent, recurrent and persistent infections.

• Type 1 diabetes:¹⁸
  • Over 60% of patients with type 1 diabetes have reasonably good health but many of the remainder develop blindness, end-stage renal disease and, in some cases, early death.
  • If a person with type 1 diabetes survives the period 10-20 years after onset of disease without ongoing complications, they have a good chance of reasonably good health.
  • Controlling blood glucose, lipids, blood pressure and weight are important prognostic factors and predict the development of long-term macrovascular and microvascular complications.
• Type 2 diabetes:¹⁹
  • Mortality is two to three times higher among people with type 2 diabetes than in the general population:
  • 75% of people with type 2 diabetes will die of heart disease and 15% of stroke.
  • The mortality rate from cardiovascular disease is up to five times higher in people with diabetes than in people without diabetes.
  • For every 1% increase in HbA1c level, the risk of death from a diabetes-related cause increases by 21%.

• Type 1: see Prevention of Type 1 Diabetes
• Type 2: see Prevention of Type 2 Diabetes

1. Giuffrida FM, Reis AF; Genetic and clinical characteristics of maturity-onset diabetes of the young. Diabetes Obes Metab. 2005 Jul;7(4):318-26. [abstract]
2. OMIM; Maturity Onset Diabetes of The Young. Online Mendelian Inheritance in Man.
3. Barrett TG, Bundey SE; Wolfram (DIDMOAD) syndrome. J Med Genet. 1997 Oct;34(10):838-41. [abstract]
4. Kondrashova A, Reunanen A, Romanov A, et al; A six-fold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med. 2005;37(1):67-72. [abstract]
5. Jasinski JM, Eisenbarth GS; Hypothesis for the pathogenesis of type 1A diabetes. Drugs Today (Barc). 2005 Feb;41(2):141-9. [abstract]
6. British Heart Foundation Statistics Website; Overall prevalence of diabetes.
7. Hu G, Rico-Sanz J, Lakka TA, et al; Exercise, genetics and prevention of type 2 diabetes. Essays Biochem. 2006;42:177-92. [abstract]
8. Tuomilehto J; Cardiovascular risk: prevention and treatment of the metabolic syndrome. Diabetes Res Clin Pract. 2005 Jun;68 Suppl 2:S28-35. Epub 2005 Apr 15. [abstract]
9. Ashcroft JS; Prevention of diabetes: lifestyle and metformin are the way forward. BMJ. 2006 Oct 28;333(7574):918-9.
10. Permutt MA, Wasson J, Cox N; Genetic epidemiology of diabetes. J Clin Invest. 2005 Jun;115(6):1431-9. [abstract]
11. Russell MA, Phipps MG, Olson CL, et al; Rates of postpartum glucose testing after gestational diabetes mellitus. Obstet Gynecol. 2006 Dec;108(6):1456-62. [abstract]
12. WHO; World Health Organisation/International Diabetes Federation, Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia, 2006.
13. No authors listed; The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30;329(14):977-86. [abstract]
14. No authors listed; Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. [abstract]
15. No authors listed; Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. [abstract]
16. Mogensen CE; Combined high blood pressure and glucose in type 2 diabetes: double jeopardy. British trial shows clear effects of treatment, especially blood pressure reduction. BMJ. 1998 Sep 12;317(7160):693-4.
17. No authors listed; Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998 Sep 12;317(7160):703-13. [abstract]
18. Hussain AN; Diabetes Mellitus, Type 1; eMedicine, July 2009.
19. Diabetes Type 2, Clinical Knowledge Summaries (2009)

• NICE; All diabetes guidelines
• Diabetes (types 1 and 2) - patient education models, NICE Technology Appraisal (2003); The clinical effectiveness and cost effectiveness of patient education models for diabetes.
• Diabetes UK; Website