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Metabolic acidosis in an Afro-Caribbean man with hyperpigmentation

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Q1: What is the metabolic condition in this case? Discuss the possible differential diagnosis

The presence of marked hyperglycaemia, ketonuria, and metabolic acidosis confirmed the diagnosis of diabetic ketoacidosis. Other possible causes of anion gap metabolic acidosis in this case include alcoholic ketoacidosis, acute pancreatitis, and acute renal failure with uraemic acidosis.

Although alcohol may have contributed to the development of ketoacidosis in this case, it is unlikely to the sole cause since plasma glucose is often low or normal in alcoholic ketoacidosis1 whereas it is markedly raised in this case. The increased serum amylase raises the possibility of acute pancreatitis which may lead to lactic acidosis. However the patient did not have abdominal pain throughout the course of his illness, and serial measurements of the serum amylase showed further elevation. The mildly increased serum amylase was more likely due to the renal impairment as amylase is renally excreted. Finally, the uraemia in acute renal failure may have contributed to the metabolic acidosis, although not to a great extent as the renal function (peak plasma urea was 21 mmol/l) of our patient improved almost immediately after treatment.

Q2: What is the dermatological diagnosis (fig 1, p 429) and which endocrine/metabolic conditions is this cutaneous sign associated with?

The presence of velvety, rough, and hyperpigmented skin in the distribution of the nape of the neck, axilla, and extensor surfaces is consistent with the clinical diagnosis of acanthosis nigricans. This cutaneous sign is associated with many endocrine and metabolic conditions as listed in box 1.2 3

Box 1: Acanthosis nigricans: endocrine/metabolic associations23

  • Obesity

  • Insulin resistance

  • Hyperinsulinaemia

  • Type 2 diabetes mellitus

  • Hypothyroidism

  • Hypogonadism

  • Hyperprolactinaemia

  • Addison's disease

  • Cushing's syndrome

  • Acromegaly

  • Polycystic ovary syndrome

  • Pituitary tumours

Q3: What further investigations may be warranted in this patient?

Further investigations should aim at excluding other causes of metabolic acidosis, screening for potential metabolic/endocrine pathologies associated with acanthosis nigricans, and predicting future insulin requirement in this patient.

In this patient endocrine investigations were unremarkable including growth hormone, insulin like growth factor-1, androgen profile, overnight dexamethasone suppression test, and 24 hour urinary free cortisol on two separate occasions. He had autonomous insulin secretion as evidenced by a fasting serum C peptide of 1231 pmol/l and in addition negative anti-islet cell and antiglutamic acid decarboxylase (GAD) antibodies.

Clinical course

This patient made good progress after initiation of treatment with intravenous fluid, insulin infusion, and prophylactic broad spectrum antibiotics. His serum amylase, plasma urea, and creatinine returned to normal. A random serum cholesterol was 4.3 mmol/l and triglyceride 2.86 mmol/l. He made an uncomplicated recovery and was discharged on Human Mixtard 30/70 36 units twice daily with dietary advice. After dietary modification, his home glucose reading was excellent (4–6 mmol/l) which led to gradual reduction and finally withdrawal of insulin. With diet control alone, his fasting glucose remained satisfactory at 6.4 mmol/l and HbA1c of 5.9% when reviewed nine months later despite no significant change in his weight.


Diabetic ketoacidosisis is common in type 1 diabetes, although it can also occur in type 2 diabetes4 5 usually in the presence of metabolic stress or pancreatic β-cell failure. Rarely, diabetic ketoacidosisis can also occur in insulin resistant states such as acanthosis nigricans6 and acromegaly.7 The aetiology of diabetic ketoacidosisis occurring in the presence of circulating insulin in these resistant states remains unclear but may be related to severe underlying insulin resistance.

The recognition of underlying insulin resistance is important in the management of these patients. Conventionally, the occurrence of diabetic ketoacidosisis signifies the requirement of lifelong insulin therapy. However, in individuals with insulin resistance long term insulin therapy may lead to weight gain, which could worsen the underlying insulin resistance. The clinical course of our patient would suggest that the glucose intolerance in this group of patients may be satisfactorily controlled with diet alone. The absence of anti-islet cell and GAD antibodies (an investigation not readily available currently in secondary care) suggest that they are unlikely to be insulin dependent in the future.8 Similar cases have previously been described in a series of African-American type 2 diabetic patients (n=79), with negative anti-islet cell and GAD antibodies who presented with hyperglycaemia with or without ketoacidosis, and were insulin independent at 3–12 months of initial presentation.9 Near normoglycaemic remission on dietary treatment alone, lasted a median of 3.5 years and about 15% of their patients had a remission greater than five years.9 It is been proposed that differences in β-cell glucose sensitivity and insulin secretion exist within ethnic populations, and the African-American type 2 diabetic subjects may have a greater β-cell insulin secretory defect.10 Close follow up of these patients and their insulin requirements is important to determine which diagnostic category, ketoacidosis onset type 2 diabetes or late onset type 1 diabetes, they fall into.

Learning points

  • Acanthosis nigricans is commonly associated with insulin resistance and type 2 diabetes.

  • Diabetic ketoacidosis, the hallmark of type 1 diabetes, may also occur in type 2 diabetes associated with insulin resistant states.

  • Normoglycaemic remission may occur in ketoacidosis onset type 2 diabetes.

  • Antibodies to islet cells and GAD antibodies may serve as a useful guide to predict future insulin dependency.

Final diagnosis

Diabetic ketoacidosis and acanthosis nigricans.


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