Diabetes Mellitus

Diabetes mellitus (DM) is a disease caused by deficiency or diminished effectiveness of endogenous insulin. It is characterized by hyperglycaemia, deranged metabolism and sequelae predominantly affecting the vasculature.
Life expectancy is reduced by 15 years in Type 1 diabetes; 5-7 years in Type 2 diabetes.
93 points are available for diabetes care in the QOF.

Prevalence

QOF data suggests that there are 1,766,391 patients registered as diabetic in England.
This gives a prevalence of 3.55%.¹
Prevalence models suggest the true prevalence is closer to 4.67%.²
The incidence of diabetes is increasing in all age groups. Type 1 diabetes is increasing in children (especially <5>

Risk Factors

People of South Asian, African and African-Caribbean and Middle-Eastern 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.

Other factors predisposing to DM

• Gestational Diabetes and impaired glucose tolerance³
• Drugs: steroids and thiazides
• Pancreatic disease: acute and chronic pancreatitis (including surgery if 90% pancreas removed),haemochromatosis, cystic fibrosis.
• Endocrine disease: Cushing's, acromegaly, phaeochromocytoma, thyrotoxicosis.
• Others: acanthosis nigricans, congenital lipodystrophy with insulin receptor antibodies, Wolfram syndrome (DIDMOAD),⁴ and glycogen storage diseases.

Genetic factors

These are complex⁵ and interact with environmental factors⁶ in a poorly understood fashion. Future research may clarify the situation.
The metabolic syndrome, akin to insulin resistance - Syndrome X- has recently come to notice and is thought of as a precursor to Type 2 diabetes. It is poorly defined and represents a heterogeneous collection of various propensities to diabetes. Its identification as a single syndrome and its relevance are uncertain.⁷ 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.^8,9,10

Classification of diabetes

Type 1 (old terms: insulin-dependent DM, IDDM)

Approximately 15% of diabetics; usually juvenile onset, but may occur at any age. It may be associated with other autoimmune disease. It is characterized by insulin deficiency.
Concordance is >30% in identical twins; 4 genes are thought to be important. One (6q) determines islet sensitivity to damage (eg from viruses or cross-reactivity from cows milk-induced antibodies). Associated with HLA DR3 and DR4 and islet cell antibodies around the time of diagnosis. Patients always need some insulin: they are prone to ketoacidosis.
Risks of developing type 1 diabetes are broadly similar in all ethnic groups, but environmental factors may also play a role.⁶The term 'Type 1a diabetes' is being applied to the development of Type 1 diabetes in adulthood. It is thought to result from a chronic auto-immune T-cell mediated islet cell destruction. Research may elucidate the underlying mechanisms, giving hope of prevention through identification and treatment of those at risk.¹¹

Type 2 (old terms: non-insulin-dependent DM, NIDDM, maturity onset DM)

Approximately 85%. Mostly an older age group and often obese. Approximately 100% concordance in identical twins. It is due to impaired insulin secretion and insulin resistance; Syndrome X. Gradual onset.
Type 2 diabetics may eventually need insulin. This does not mean that type 1 diabetes has developed.
Insulin is likely to be needed in those with:

• Ketonuria
• Glucose >25mmol/l
• Sudden onset weight loss, dehydration, ketoacidosis

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.^12,13

Presentation

Patients may be asymptomatic.
Acute:

• Ketoacidosis - unwell, hyperventilation, ketones on breath.
• Few weeks of weight loss, polyuria and polydipsia.

Subacute:

• History as above, but longer.
• In addition lethargy, infection, pruritis vulvae, boils.

Complications may be the presenting feature: infections, neuropathy and ulcers, retinopathy, arterial disease (eg MI or claudication).

Diagnosis

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

• They have symptoms of diabetes (unexplained weight loss, polyuria, polydypsia), plus random blood glucose (RBG) >11.1mmol/l.¹⁴
• The 2 hour plasma glucose is >11.1mmol/l, as part of a standard or abbreviated OGTT (exact diagnostic criteria are discussed in glucose tolerance tests).

Management

Global aims of diabetic programmes are detailed in the St Vincent's declaration.

• Acute presentation: see Diabetic Emergencies.
• Subsequent management of the new diabetic: see The Newly Diagnosed Diabetic.
• Long term management: see Managing Diabetes in General Practice, Diabetes and hypoglycaemic agents and insulin regimes.
• Specific circumstances: Precautions with Diabetic Patients Undergoing Surgery, Diabetes and Intercurrent Illness and Diabetes in Pregnancy.

The aims of treatment is the avoidance of complications, which include hypoglycaemia as well as the long term consequences of hyperglycaemia.
Strict plasma glucose control does reduce renal, CNS and retinal damage, although macrovascular disease is unaffected.^15,16,17
However, a balance is required for each patient between lower blood glucose readings and the risk of hypoglycaemia.
Interestingly, tight blood pressure control is as effective in reducing microvascular disease, but also reduces macrovascular disease, and mortality.^18,19
This emphasizes the importance of a global assessment of an individual's cardiovascular risk: glucose, blood pressure, cholesterol, and smoking history. Don't treat DM in isolation.
Audit the care you provide.

British Diabetic Association Recommendations (Implications from UKPDS for the care of people with type 2 diabetes) Blood pressure levels of ≤130/80 mm Hg HbA1c levels of 6.5% or below Fasting blood glucose levels of 4 - 7 mmol/l Self monitored blood glucose levels before meals between 4 and 7 mmol/l Total cholesterol level should be ≤4.0 mmol/l, LDL level ≤2.0 mmol/l20

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Document references

1. QOF Database; 2006
2. King H, Aubert RE, Herman WH; Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. [abstract]
3. 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]
4. Barrett TG, Bundey SE; Wolfram (DIDMOAD) syndrome. J Med Genet. 1997 Oct;34(10):838-41. [abstract]
5. Permutt MA, Wasson J, Cox N; Genetic epidemiology of diabetes. J Clin Invest. 2005 Jun;115(6):1431-9. [abstract]
6. 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]
7. Aguilar-Salinas CA, Rojas R, Gomez-Perez FJ, et al; The metabolic syndrome: a concept hard to define. Arch Med Res. 2005 May-Jun;36(3):223-31. [abstract]
8. Hu G, Rico-Sanz J, Lakka TA, et al; Exercise, genetics and prevention of type 2 diabetes. Essays Biochem. 2006;42:177-92. [abstract]
9. 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]
10. Ashcroft JS; Prevention of diabetes: lifestyle and metformin are the way forward. BMJ. 2006 Oct 28;333(7574):918-9.
11. Jasinski JM, Eisenbarth GS; Hypothesis for the pathogenesis of type 1A diabetes. Drugs Today (Barc). 2005 Feb;41(2):141-9. [abstract]
12. 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]
13. OMIM. Maturity Onset Diabetes of The Young
14. WHO; World Health Organisation/International Diabetes Federation, Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia, 2006.
15. 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]
16. 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.; Lancet. 1998 Sep 12;352(9131):854-65. [abstract]
17. 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]
18. 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.
19. 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]
20. JBS2; JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice; 2005

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Internet and further reading

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