ANSWERS
CASE 17: A ROUTINE ‘HEALTH CHECK’ FOR A 55-YEAR-OLD MAN
A 55-year-old man presents to his GP for his annual check-up. He has a history of hyperten
sion, which is controlled by amlodipine, and hyperlipidaemia, for which he takes a statin. He does not complain of any particular symptoms, but notes that he has been urinating more frequently. He wonders whether this may be an early sign of diabetes, as both his brothers have recently been diagnosed with this condition. He has a family history of cardiovascular disease, with both his parents having suffered a heart attack in their 60s. He recently stopped smoking but has a 35 pack-year history.
Examination
Body mass index (BMI) is 28. Cardiovascular, respiratory, abdominal and neurologic exami
nations are unremarkable. Digital rectal examination reveals a small and benign-feeling prostate.
QUESTIONS
1. What investigations may be used to diagnose diabetes in this gentleman?
2. Describe the pathophysiology of type 2 diabetes.
3. What are the complications of diabetes, and what do you know about their aetiology?
4. Discuss the overall principles of management of this patient, assuming he is found to be diabetic.
DOI: 10.1201/9781003242697-18 49
100 Cases in Clinical Pathology and Laboratory Medicine 50
ANSWERS
Type 2 diabetes mellitus is predominantly a disease of the older population and accounts for 90% of cases of diabetes. It may be diagnosed through three tests: (1) fasting glucose levels, (2) glucose tolerance test and (3) glycated haemoglobin levels. Additionally, in this case, test
ing the urine for glucose might be useful, though it must be remembered that around 10% of cases of glycosuria are not caused by hyperglycaemia.
Fasting glucose levels were the easiest way in which to test for diabetes until glycated haemo
globin (HbA1c) assays became available. The World Health Organization (WHO) criteria for diabetes require a fasting glucose level of ≥7 mM, since that is the level above which the microvascular complications of diabetes become detectable. An oral glucose tolerance test (measuring plasma glucose 2 hours after a standardised glucose load, with levels ≥11.1 mM being diagnostic of diabetes) is a more sensitive marker of glucose dysregulation but is more expensive and less reproducible. More recently, the use of HbA1c levels have been used in diagnosing type 2 diabetes. HbA1c measures the non-enzymatic glycation of amino acids on the haemoglobin molecule and reflects the glycaemic state over the prior 8–12 weeks. Normal levels are between 4% and 6%, with the WHO recognising a threshold of 6.5% as the cut-off point for diagnosing type 2 diabetes.
The two main metabolic defects that underlie type 2 diabetes are insulin resistance and sub
sequent pancreatic β-cell dysfunction. The former is caused by both quantitative and quali
tative changes in insulin signalling, such as reduced receptor tyrosine kinase activity, which is strongly linked to obesity (‘lipotoxicity’). Initially, insulin resistance is compensated for by pancreatic β-cell hypersecretion of insulin; however, there is eventual decompensation, the mechanisms of which remain unclear, but are likely linked to lipotoxicity and ‘glucotoxicity’.
It is also important to be aware of the genetic link in type 2 diabetes, which is stronger than in type 1 diabetes.
Life expectancy in diabetics is reduced by 5–10 years compared to non-diabetics. The major causes of excess mortality are cardiovascular disease, renal problems and infection. Hence, the complications of diabetes are just as important to monitor as glycaemic control itself.
Broadly speaking, these complications may be categorised as either microvascular (disease of small blood vessels) or macrovascular (large-vessel disease). Microvascular complications include retinopathy, nephropathy and neuropathy, while the predominant macrovascular complications are cardiovascular, cerebrovascular and peripheral vascular disease.
The principal mechanism underlying macrovascular complications is accelerated athero
sclerosis of large vessels, leading to a higher risk of thrombosis and occlusion, while the basic pathophysiology underlying microangiopathy is thickening of capillary basement mem
branes in the retina, kidneys and vaso nervorum. In the kidney, these thickened capillaries are more leaky than normal to plasma proteins, giving rise to microalbuminuria. Similarly, in the eyes, microangiopathy gives rise to non-proliferative or proliferative retinopathy.
Indeed, diabetes is the most common cause of blindness in individuals under 65 years of age.
Given the burden of disease that diabetes imposes, its management is multi-faceted.
Patient education and dietary measures form the basis of conservative management, par
ticularly in diabetics whose β-cells are able to compensate. Oral anti-diabetic agents that aim to either stimulate insulin secretion (e.g., sulphonylureas) or increase insulin sensitivity (e.g., metformin) may be required to optimise glycaemic control, and the last resort is insulin.
However, it is important to remember that diabetes management is not just about control
ling sugar levels but that hypertension and hyperlipidaemia need to be aggressively managed
Case 17: A Routine ‘Health Check’ for a 55-Year-Old Man 51
too. Additionally, patients with nephropathy require angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonist therapy and regular diabetic eye screening is needed to monitor for retinopathy.
KEY POINTS
• Type 2 diabetes is the most common form of diabetes and may be diagnosed via measurement of fasting glucose levels, an oral glucose tolerance test, or HbA1c levels.
• The pathophysiology underlying the disease stems from insulin resistance and eventual pancreatic β-cell dysfunction and decompensation.
• Management of type 2 diabetes involves not only aggressive glycaemic control but also minimising cardiovascular risk factors and possible renal and retinal disease.
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