Clinical Case Studies - Diabetes

Question 1

What is Diabetes Mellitus?

Answer 1

Metabolic condition in which the patient has hyperglycemia due to insulin insensitivity or decreased insulin secretion.

Question 2

How would you investigate for Diabetes?

Answer 2

• Blood glucose
• Urine glucose and ketones
• U&Es, including serum bicarbonate concentration
• Venous pH and pCO₂
• Calcium, phosphorus, and magnesium
• Diabetes-associated antibodies – insulin auto-antibodies, islet cell antibodies, and zinc transporter antibodies
• C-peptide levels – byproduct of insulin production

Question 3

How is diabetes diagnosed?

Answer 3

Diagnostic criteria for diabetes

• Fasting plasma glucose ≥126 mg/dL (7 mmol/L) on more than one occasion. Fasting is defined as no caloric intake for at least eight hours.
• Random venous plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia.
• Plasma glucose ≥200 mg/dL (11.1 mmol/L) measured two hours after a glucose load of 1.75 g/kg (maximum dose of 75 g) in an oral glucose tolerance test.
• Most children and adolescents are symptomatic and have plasma glucose concentrations well above ≥200 mg/dL (11.1 mmol/L); thus, an oral glucose tolerance test is seldom necessary to diagnose T1DM.
• Glycated hemoglobin (A1C) ≥6.5 percent
• This criterion is more useful to diagnosis of type 2 diabetes mellitus (T2DM) in adults and should be confirmed by hyperglycemia.

Question 4

How does hyperglycemia cause sequelae of diabetes?

Answer 4

• Hyperglycaemia
• Mitochondrial oxidative stress via increase in oxygen free radicals
• Increases inflammatory signaling cascades
• Activation of pro-inflammatory cytokines
• Inflammation
• Generation of Nephropathy, Retinopathy and Neuropathy
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Question 5

What is Type 1 DM?

Answer 5

• Autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans
• Occurs in genetically susceptible subjects
• Probably triggered by one or more environmental agents
• Usually progresses over many months or years during which the subject is asymptomatic and euglycemic.
• Long latent period is a reflection of the large number of functioning beta cells that must be lost before hyperglycemia occurs
• Often a disease of childhood

Question 6

What are the pathological stages of T1DM?

Answer 6

• Stage 1 – Multiple islet autoantibodies, normal blood glucose, and presymptomatic
• Stage 2 – Multiple islet autoantibodies, raised blood glucose, and presymptomatic
• Stage 3 – Islet autoimmunity, raised blood glucose, and symptomatic
• Stage 4 – Longstanding T1DM

Question 7

What are risk factors for developing T1DM?

Answer 7

• Genetics
• Viral infections, particularly respiratory or enterovirus infections
• Diet
• Higher socioeconomic status
• Obesity
• Vitamin D deficiency
• Perinatal factors such as maternal age, history of preeclampsia, and neonatal jaundice
• High birth weight for gestational age and lower gestational age at birth may increase the risk for T1DM

Question 8

How does T1DM Present?

Answer 8

• Classic new onset - chronic polydipsia, polyuria, and weight loss with hyperglycemia and ketonemia (or ketonuria), blurred vision
• Diabetic ketoacidosis (DKA) - dehydration, shock, hyperventilation (Kussmaul), drowsiness, abdominal pain
• Silent (asymptomatic) incidental discovery

Question 9

What is DKA?

Answer 9

Diabetic ketoacidosis - Emergency presentation of T1DM

• Hyperglycemia (blood glucose 11 mmol/L)
• Metabolic acidosis (venous pH <7.3 or serum bicarbonate 15 mmol/L
• Ketosis (presence of ketones in the blood or urine)

Question 10

What is T2DM?

Answer 10

• Hyperglycemia usually due to progressive loss of insulin secretion from the beta cell superimposed on a background of insulin resistance, resulting in relative insulin deficiency
• Mostly adults

Question 11

What are the risk factors for T2DM?

Answer 11

• Family history of diabetes mellitus in a first-degree relative
• High risk race/ethnicity (eg, African, Latino, Asian, or Native American descent)
• Sedentary lifestyle
• Central adiposity/poor diet
• Polycystic ovary syndrome (women)

Question 12

What is the pathophysiology of T2DM?

Answer 12

The pathogenesis of type 2 diabetes is multifactorial .

• Insulin resistance – The underlying cause of the insulin resistance has traditionally been attributed to predominantly “environmental” factors related to overeating, sedentary lifestyle, and resulting overweight and obesity, with less prominent contributions from aging and genetics.
• Impaired insulin secretion – The defective insulin secretion is largely a result of genetic influences and the programming of the beta cell mass and function in utero. Additionally, hyperglycemia itself can impair pancreatic beta cell function and exacerbate insulin resistance (“glucotoxicity”), leading to a vicious cycle of hyperglycemia causing a worsening metabolic state.

The mechanism by which obesity induces insulin resistance is poorly understood.

Signalling factors from body fat (leptin. adiponectin) can reduce response to insulin

Question 13

How can T2DM present?

Answer 13

• The majority of pare asymptomatic, and hyperglycemia is noted on routine laboratory evaluation, prompting further testing.
• Polyuria, polydipsia, nocturia, blurred vision, and weight loss.
• DKA (rarely)
• Hyperosmolar hyperglycemic state

Question 14

What is Hyperglycemic hyperosmolar state?

Answer 14

Hyperglycemic hyperosmolar state — DKA must be distinguished from hyperglycemic hyperosmolar state (HHS), which is characterized by:

• Marked hyperglycemia (plasma glucose >33.3 mmol/L)
• Minimal acidosis (venous pH >7.25 or arterial pH >7.3 and serum bicarbonate >15 mmol/L)
• Absent to mild ketosis
• Marked elevation in serum osmolality (effective osmolality >320 mOsm/kg)

HHS occurs most commonly in adults with poorly controlled type 2 diabetes

Question 15

How can you distinguish between T1 and T2DM?

Answer 15

• No set of criteria or diagnostic test can consistently distinguish between T1DM and T2DM. Therefore, differentiating between the two types is based upon a combination of the clinical presentation and history, often supported by laboratory studies.

Clinical characteristics:

• Body habitus – Patients with T2DM are usually obese. In Children with T1DM are usually not obese and often have a recent history of weight loss, although up to 25% are overweight.
• Age – Patients with T2DM generally present after the onset of puberty, whereas those with T1DM often present at an earlier age.
• Insulin resistance – Patients with T2DM frequently have acanthosis nigricans (a sign of insulin resistance), hypertension, dyslipidemia, and polycystic ovary syndrome (in girls). These findings are less likely in children with T1DM.
• Family history – Up to 10 percent of patients with T1DM have an affected close relative, whereas 75 to 90 percent of those with T2DM have an affected close relative.

Laboratory testing:

• Antibodies – AT1DM is suggested by the presence of circulating, islet-specific pancreatic autoantibodies. However, the absence of pancreatic autoantibodies does not rule out the possibility of T1DM.
• Insulin and C-peptide levels – High fasting insulin and C-peptide levels suggest T2DM. Levels are inappropriately low or in the normal range relative to the concomitant plasma glucose concentration in T1DM.