Lecture 11

Lecture 11. Basic principles of diabetes
1. Describe the diagnostic criteria for diabetes mellitus.
Fasting plasma glucose >126 mg/dl, on ≥2 occasions – Gold standard
Glucose tolerance test (administer 75 g glucose and get 2hr plasma glucose ≥200 mg/dl) – Research only, not used clinically
Hemoglobin A1c increased – Used to assess effectiveness of treatment, not diagnosis

2. List the three acute-phase and six late-phase risks from diabetes and how the risks can be minimized.
Acute - Poor control can cause diabetic ketoacidosis (type 1) or non-ketotic hyperosmolar coma (type 2). Too tight control can cause hypoglycemia.
Late - Microvascular (retinopathy, nephropathy, neuropathy). Macrovascular (coronary artery disease, cerebrovascular disease, peripheral vascular disease)

3. Given a clinical presentation, be able to diagnose:
a. Type 1, insulin dependent diabetes mellitus
Hyperglycemia (see above)
Hx – Polyuria, polydipsia, polyphagia
Weight loss, thin patient
Young patient
Labs – Loss of insulin and C-peptide
Positive anti-islet antibodies
May present in DKA

b. Type 2, non-insulin dependent diabetes mellitus
Hyperglycemia
Hx – Polyuria, polydipsia, polyphagia
Mild weight loss if any, obese patient
Older patient
Labs – Normal/increased insulin and C-peptide
Possible proteinuria
May present in hyperosmolar coma – massive glucose

4. Describe the pathophysiology of types 1 and 2 diabetes mellitus in terms of causes for abnormal beta cell activity, autoimmunity, and hormone levels.
Type 1 – is due to autoimmune destruction of pancreatic beta cells, thought to occur after a precipitating environmental event (viral infection). Beta cell mass, insulin secretion, and C-peptide (a marker) all decrease. The patient goes from clinically silent to abnormal glucose tolerance to non-ketoacidotic diabetes to ketoacidotic diabetes.
Some patients can briefly return to normoglycemia even after presenting in ketoacidosis – the honeymoon period – because they still have enough insulin to prevent hyperglycemia. Then there is another precipitating event (e.g., infection, surgery), which increases epinephrine and norepinephrine release, which diminish insulin secretion (in normal and prediabetic people). After this stress is over there can be another honeymoon period in which the remaining beta cells are able to control blood glucose for an additional (short) period.

Type 2 – is due to insulin resistence. Obesity leads to insulin resistance; most patients with NIDDM are obese. This causes the beta cell to have to increase glucose secretion; however, over time the beta cell fails and can no longer produce the levels of insulin necessary to control blood glucose. This failure is due to either genetic reasons or because of toxicity of elevated glucose and free fatty acids. When the beta cells are unable to compensate is when the patient presents with overt diabetes. However, this form of diabetes is not associated with DKA because there is enough insulin to prevent that; instead they are at risk of hyperosmolar coma.
Caloric excess leads to hyperinsulinemia leads to increased SREBP1c leads to increased lipogenesis leads to increased adiposity (obesity) leads to ectopic fat deposition leads to insulin resistance leads to beta cell lipotoxicity leads to hyperglycemia (diabetes)