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Diabetes Clinical Case Series, Excerpt #7, Endocrinology and Diabetes

CCU_Endocrinology_and_Diabetes

Ivy, a 29-year-old woman, presents with a short history of polyuria and polydipsia. What differential diagnosis would you be thinking of?

The differential diagnosis includes:

• Diabetes mellitus
• Hypercalcaemia
• Chronic renal failure
• Diabetes insipidus
• Psychogenic polydipsia

Her blood tests done by her GP earlier showed:

  • Glucose 20 mmol/L
  • Sodium 131 mmol/L
  • Potassium 4.4 mmol/L
  • Urea 5.4 mmol/L
  • Creatinine 76 mmol/L
  • Calcium 2.34 mmol/L

What questions would you ask this patient?

Ivy has high plasma glucose levels indicating a diagnosis of diabetes. It is important at this stage to differentiate between type 1 diabetes (T1DM) and T2DM. Questions to ask:

  • How long have the symptoms of polyuria and polydipsia been present?
    • A short history of symptoms (days to weeks) is suggestive of T1DM
    • A long history of symptoms (months) or no symptoms is suggestive of T2DM
  • History of rapid weight loss is strongly suggestive of T1DM
  • Family history of diabetes
    • Family history of T1DM or autoimmunity (i.e.thyroid disease, pernicious anaemia) suggests a genetic predisposition to T1DM
    • Family history of diabetes at young age not requiring insulin or diabetes inherited in an autosomal dominant manner is suggestive of Maturity Onset Diabetes of the Young (MODY)

What test would you ask the nurse to perform that may help to differentiate between T1DM and T2DM?

Urine dipstick for ketones
  • Heavy ketonuria is consistent with T1DM
  • Absence of ketonuria does not rule out T1DM
What else would you like to know?

The weight/BMI of the patient

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Ivy tells you that she had osmotic symptoms for 7–10 days, associated with 4 kg weight loss. Her sister has vitiligo but there is no other family history of note. Her BMI is 22 kg/m2.

Her urine dipstick shows:

  • Glucose 3+
  • Ketone 3+
  • Nitrate negative
  • WBC negative

What is the most likely diagnosis?

The most likely diagnosis is T1DM supported by:

  • Short history of symptoms
  • Significant weight loss
  • Thin patient
  • Family history of autoimmunity (vitiligo)

In unclear cases, can you do a blood test to help to differentiate between T1DM and T2DM?

  • Glutamic acid decarboxylase (GAD) and islet cell antibodies are positive in the majority of T1DM patients (around 80%)
  • A negative antibody test does not rule out the diagnosis of T1DM
What treatment would you start?

Ivy should be immediately started on insulin.

  • Most patients can be managed on an out-patient basis.
  • Admission should be considered for patients who look unwell or in the presence of abdominal pain/vomiting to rule out the possibility of diabetic ketoacidosis.

Ivy is started on Novomix 30, 12 units in the morning and 6 units in the evening and the dose is gradually titrated up to 24 and 14 units over a period of 6 weeks. Her glycemic control was initially very good on these doses of insulin, but 4 months after diagnosis she had to drastically reduce the dose of her insulin to 8 and 4 units due to recurring hypoglycemic attacks.DCMS174CG2

 
Why did this happen?

The pancreas of patients with T1DM may partially recover after the initial diagnosis resulting in decreased insulin requirement. This is known as the honeymoon period. 

What do you need to ensure with any diabetes patient during a routine review?

  • Ensure adequate control of blood sugar
    • Measure HbA1c levels and aim for <6.5%
    • Check glucose diary
  • Look for signs of microvascular disease:
    • Eyes: retinopathy (retinal screening once a year)
    • Kidney: check for microalbuminuria (request urinary albumin/creatinine ratio once a year)
    • Feet: examine for neuropathy (monofilament test and vibration sense once a year)
  • Ensure prevention/treatment of macrovascular complications:
    • Treat hypertension
    • Treat hyperlipidaemia: patients with diabetes above the age of 40 are usually started on lipid lowering treatment with a statin no matter what their plasma cholesterol levels are
    • Antiplatelet treatment (aspirin or clopidogrel) in high risk subjects
    • Aggressive measures for prevention/treatment from macrovascular disease should be implemented in the presence of microvascular complications
What are the types of diabetes?

Traditionally, young patients with diabetes were more likely to have T1DM. However, due to the recent problem of obesity, T2DM can be now seen at a very young age (even children).

Other types of diabetes include:

  • Maturity Onset Diabetes of the Young (MODY, up to 3% of T2DM)
    • This is a monogenic form of diabetes (due to a single gene defect)
    • Has an autosomal dominant mode of inheritance
    • Patients are usually young and can be misdiagnosed as having T1DM
  • Latent Autoimmune Diabetes of Adults (LADA)
    • An autoimmune form of diabetes occurring at an older age
    • Patients are usually slim
    • Patients are initially managed by oral hypoglycemic agents but usually require insulin early after diagnosis (LADA is commonly a retrospective diagnosis)
  • Gestational diabetes
    • Occurs during pregnancy
    • Disappears after giving birth
    • Subjects with a history of gestational diabetes are at increased risk of T2DM in the future
  • Secondary diabetes
    • Destruction of the pancreas: pancreatitis, pancreatic tumour, infiltrative disease (haemochromatosis)
    • Endocrine abnormalities: acromegaly, Cushing’s disease, pheochromocytoma, hyperthyroidism (rare)
  • Associated with genetic syndromes
    • Down’s syndrome
    • Turner’s syndrome
    • Lawrence-Moon-Biedl syndrome
    • Prader-Willi syndrome
  • Drug-induced
    • Steroids

Ivy’s father, Andrew aged 62, presents a few months later to his GP, stating that his daughter checked his blood sugar with her glucose meter and found it to be elevated. He is asymptomatic and overweight with a BMI of 29.9. He has no past medical history of note and his urine dipstick shows:

  • Glucose 3+
  • Ketone trace
  • Nitrate negative
  • WBC negative
What test would you request?

Fasting plasma glucose on two occasions.

  • Diabetes is usually confirmed by checking fasting glucose twice, particularly in individuals who are asymptomatic
  • In subjects with classical symptoms, one glucose sample is enough to confirm the diagnosis

His blood tests showed:

  • Fasting glucose: 10.3 and 11.6 mmol/L
  • HbA1c: 8.6%
  • U&Es normal
What is the likely diagnosis?

This gentleman has T2DM supported by:

  • High fasting plasma glucose (more than 7.0 mmol/L on two occasions)
  • Overweight
  • Absence of symptoms
  • Urine dipstick negative for ketones

Rarely, some patients are misdiagnosed as having T2DM, when they have a secondary form of diabetes, and, therefore, the above list of causes of secondary diabetes should be kept in mind when assessing a new patient with suspected T2DM.

What medical treatment would you initiate to control his blood glucose levels?

None. Instead, advise the patient to:

  • Change to a healthy diet
  • Regular exercise
  • Try to lose weight

Andrew implements your suggestions and is reviewed 3 months later. He has lost 4 kg in weight and his HbA1c is now 6.8%.

What would you do?

Congratulate Andrew and encourage him to continue with his program of:

  • Diet
  • Exercise

He is reviewed 18 months later. Despite continuing with diet and exercise, his HbA1c has risen to 8.1%.

What would you do to control his blood sugar?

Andrew needs to be started on antidiabetic treatment. The preferred first-line agent in overweight T2DM patients is metformin (Glucophage).

Andrew is well on metformin for 2 years but his diabetes control subsequently deteriorates and his HbA1c rises to 8.9%.

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What would you do now?

Andrew can be started on one of the following drugs:

  • A sulphonylurea: this group of drugs stimulate insulin secretion by the pancreas. Commonly used drugs include:
    • Gliclazide
    • Glimepiride
  • A thiazolidinedione: this group of drugs act as insulin sensitizers and seem to have cardioprotective properties. Commonly used drugs include:
    • Rosiglitazone
    • Pioglitazone

What are the two main drawbacks of sulphonylureas?

  • Weight gain due to stimulation of insulin secretion
  • Hypoglycemia

What is the main contraindication for the use of thiazolidinediones?

  • Heart failure is the main contraindication as these agents may cause fluid retention, thereby worsening existing heart failure

When do you use insulin in type 2 diabetes?

  • Failure of oral therapy
  • Hospital admission
  • Infection
  • Myocardial infarction
  • Pregnancy, as oral hypoglycemics are contraindicated
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Figure 58 Treatment of type 2 diabetes. Metformin is usually the first-line agent except in those with contraindication or intolerance. Oral hypoglycemic agents can be used in combination therapy (even as triple therapy). Insulin can be used in combination with metformin or a sulphonylurea and even pioglitazone. New agents that have been recently released include glucagon-like peptide analogues (injections) and DPP-4 inhibitors (oral), which can be used as second- to fourth-line agents.

Apart from antidiabetic agents, what other drugs are available that may help to control blood sugar?

  • Slimming tablets such as:
    • Sibutramine
    • Orlistat
    • Rimonabant
  • Acarbose which inhibits glucose absorption Treatment of type 2 diabetes is summarized in Fig. 58
 

CASE REVIEW 

Ivy is a young woman presenting with a short history of polyuria and polydipsia. Her blood tests are consistent with a new diagnosis of diabetes. A detailed history is taken to establish the type of diabetes. A short history of symptoms in a lean patient, weight loss, a family history of autoimmunity and ketonuria all suggest a diagnosis of type 1 diabetes. In unclear cases, autoantibody measurement and insulin levels can be helpful to distinguish between different types of diabetes. Ivy is started on insulin treatment, which controls her diabetes well. However, her insulin requirements subsequently decrease due to partial recovery of the pancreas, often known as the honeymoon period, which is a temporary phenomenon.

Andrew, Ivy’s father, measures his blood sugar using his daughter’s glucose meter and his capillary glucose is found to be elevated. He is asymptomatic, overweight and his urine test shows absence of ketonuria. His fasting glucose is checked on two occasions (as he is asymptomatic) and found to be elevated confirming a diagnosis of diabetes. Andrew is overweight, asymptomatic with no ketonuria consistent with a diagnosis of type 2 diabetes. Andrew initially manages to control his diabetes with diet, exercise and weight loss. His diabetes control deteriorates 18 months later and he is started on metformin treatment, which is the first-line agent in overweight T2DM patients. His diabetes control deteriorates again and, traditionally, either a sulphonylurea or a thiazolidinedione can be given at this stage. Newer agents, including GLP-1 analogues and DDP-4 inhibitors, can also be used as second-, third- or fourth-line treatments.

It should be remembered that the majority of diabetes patients develop vascular complications and it is important to treat a cluster of risk factors, rather than blood sugar alone, in these patients to prevent long-term complications.These risk factors include hypertension, microalbuminuria, dyslipidaemia and increased thrombosis potential.

 

 

Ramzi Ajjan, MRCP, Med Sci, PhD, Senior Lecturer and Honorary Consultant in Diabetes and Endocrinology, Department of Health Clinician Scientist, The LIGHT Laboratories, University of Leeds, Leeds, UK
 

A John Wiley & Sons, Ltd., Publication This edition first published 2011 © 2011 by John Wiley & Sons, Ltd.

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