“Basics” of diabetology

Page created on January 11, 2021. Not updated since.

Before our exam in diabetology, a teacher at the department said that we should focus on the following, which are “considered to be the basics of diabetology”:

  • Diagnostic criteria of diabetes and prediabetic conditions with exact values!
  • The classification of diabetes mellitus with subgroups, where needed
  • The acute and chronic complications of diabetes mellitus
  • Therapy of type 2 diabetes: major approaches and types of antidiabetic medications, pros and cons to the individual groups

I wrote short notes for each of these. The notes cover most questions we were asked at the exam.

Diagnostic criteria of diabetes and prediabetic conditions with exact values!

Test method

Healthy

Prediabetes

Diabetes mellitus

Random plasma glucose (RPG)

≥ 11,1 mM

Oral glucose tolerance test (OGTT)

< 7,8 mM

7,8 – 11,1 mM

= impaired glucose tolerance (IGT)

≥ 11,1 mM

Fasting plasma glucose (FPG)

< 6,1 mM

6,1 – 7,0 mM

= impaired fasting glucose (IFG)

≥ 7,0 mM

HbA1c

< 5,7 %

(< 39 mmol/mol)

5,7 – 6,5 %

(39 – 48 mmol/mol)

≥ 6,5 %

(> 48 mmol/mol)

Random plasma glucose > 11,1 mM is only diagnostic for DM in patients who have symptoms of DM! If they’re asymptomatic, elevated random plasma glucose is not diagnostic.

OGTT involves measuring blood glucose before and 2 hours after ingestion of 75 g oral glucose in a patient who has fasted for 12 hours, usually from the day before. It is mostly used to screen for gestational diabetes.

The classification of diabetes mellitus with subgroups, where needed

  • Type 1 diabetes mellitus
    • Type 1A (autoimmune) (almost all cases of T1D)
    • Type 1B (idiopathic) (autoantibodies absent; very rare)
    • Latent autoimmune diabetes in adults (LADA)
  • Type 2 diabetes mellitus
  • Other types of diabetes mellitus
    • Maturity onset diabetes of the young (MODY)
    • Pancreoprivic diabetes (diseases of exocrine pancreas)
      • Cystic fibrosis
      • Chronic pancreatitis
      • Hereditary haemochromatosis (bronze diabetes)
    • Endocrinopathies
      • Cushing syndrome
      • Acromegaly
    • Drug-induced diabetes
      • Glucocorticoids
      • Antipsychotics
      • +++
  • Gestational diabetes

The acute and chronic complications of diabetes mellitus

Acute complications: hypoglycaemia

Hypoglycaemia occurs more commonly in type 1 diabetes than type 2, although it occurs in both. It can occur when taking too much antidiabetic or insulin, after skipping meals, after exercising, after stress, after alcohol consumption, etc. Insulin, sulfonylureas and meglitinides are the antidiabetics with highest risk for hypoglycaemia.

Hypoglycaemia causes symptoms directly related to decreased glucose supply to the brain (neuroglycopaenic symptoms), as well as symptoms related to the autonomic response to hypoglycaemia (autonomic symptoms). The neuroglycopaenic symptoms include confusion, dizziness, weakness, and possibly delirium. The autonomic symptoms include tremor, palpitations, anxiety, sweating, and hunger.

Mild hypoglycaemia is treated by giving complex carbohydrates like bread. Moderate hypoglycaemia is treated by giving oral liquid glucose. Severe hypoglycaemia is treated by administering IV glucose. If IV access is not available, intramuscular or intranasal glucagon is used.

Acute complications: hyperglycaemic crises

The two hyperglycaemic crises in diabetes are diabetic ketoacidosis (DKA) and hyperosmolar-hyperglycaemic state (HHS). Both are characterised by severe hyperglycaemia, causing osmotic diuresis with resulting dehydration and loss of electrolytes. Hyperglycaemic crises can be triggered by infections, cardiovascular accidents, alcohol abuse, or inappropriate antidiabetic therapy. DKA may be the first manifestation of type 1 diabetes.

Diagnosis of DKA is based on the presence of:

  • Hyperglycaemia
    • Usually between 10 – 15 mM
  • High anion gap metabolic acidosis
    • Acidosis (pH < 7,30)
    • Elevated anion gap (> 10 mM)
    • Decreased bicarbonate (< 18 mM)
  • Ketonuria

Diagnosis of HHS is based on the presence of:

  • Hyperglycaemia
    • Usually > 33,3 mM
  • Elevated serum osmolality
  • Normal pH
  • Normal anion gap

Physical examination may show decreased skin turgor, Kussmaul breathing (in DKA), tachycardia, hypotension, and abdominal pain. Glucometers should not be used to measure blood glucose in hyperglycaemic crises as they can’t measure above around 15 mM.

Treatment of a hyperglycaemic crisis involves getting IV access. Administer 1 litre physiological saline in the first hour, and later continue administering fluids according to the fluid deficit. If potassium level is < 3,3 mM, it must be repleted before administering insulin. Potassium must be closely monitored and should be kept above 5,3 mM. When potassium is above 5,3 mM, administer 0,1 units/kg insulin per hour. Don’t let blood glucose level go below 8 mM; if it does, add glucose infusion.

Bicarbonate should only be used if pH goes below 7. Electrolytes, pH, creatinine, and glucose should be monitored regularly (every 2 – 4 hours) during the treatment.

Chronic complications

Patients with diabetes mellitus, especially type 2, experience both macrovascular and microvascular complications. The best way to prevent these complications is by strict long-term glucose control, as well as control of blood pressure and lipid levels, use of aspirin, and smoking cessation.

The macrovascular complications include coronary heart disease, cerebrovascular disease, and peripheral artery disease.

The microvascular complications include diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, and diabetic foot.

To prevent chronic complications, patients with diabetes should be regularly examined, 2 – 4 times yearly. The body parameters, examination of the feet, HbA1c, and blood pressure should be measured. A detailed eye examination should be done annually. Urinary albumin should also be measured annually.

Patients with type 2 diabetes also have increased risk for some cancers, especially liver and pancreas.

Therapy of type 2 diabetes: major approaches and types of antidiabetic medications, pros and cons to the individual groups

All patients with type 2 diabetes should participate in a diabetes self-management education program, which provides the patient information on the proper lifestyle modifications, including instruction on proper nutrition and physical activity. Lipid levels and blood pressure should also be treated, if abnormal.

Diet

Proper diet is one of the most important therapies in type 2 diabetes. Good dietary habits normalize body weight and decreases insulin resistance. An ideal diet contains approx. 25 – 35 kcal/kg of bw per day, with carbohydrates accounting for 50% of those calories.

Treatment with antidiabetic drugs

Most patients diagnosed with type 2 diabetes should begin pharmacological treatment at the time of diagnosis. The exception to this is those patients who are highly motivated and committed to using only lifestyle modification, which can be tried for 3 – 6 months before evaluating the response.

All oral antidiabetics are contraindicated during pregnancy. Pregnant women must be treated with insulin for the whole duration of the pregnancy.

Metformin

Metformin is the first-line antidiabetic, and should be used in all type 2 diabetics who have no specific contraindications. Metformin is effective, safe, does not increase weight, does not cause hypoglycaemia, is well tolerated, and is cheap. The starting dose is 500 – 850 mg/day, which is slowly uptitrated to 2000 or 2550 mg/day.

Unfortunately, metformin has many contraindications. It is contraindicated in kidney failure (GFR < 30), liver failure, hypoxic heart failure (NYHA III, IV), hypoxic respiratory failure, and pancreatitis. It must also be paused a couple of days before surgery and before x-ray examinations with iodine contrast, and resumed two days later as long as the renal function is still good enough (> 30 mL/min). Disregarding these contraindications has a high risk of causing severe lactic acidosis.

Overview of antidiabetics

GLP-1 receptor agonists and SGLT-2 inhibitors have proven benefit on atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and heart failure (HF). Patients with either of these diseases should receive metformin (unless contraindicated) as well as either a GLP-1 receptor agonist or an SGLT-2 inhibitor as first-line treatment.

In patients who don’t reach the target HbA1c with the first-line treatment, another oral antidiabetic should be added. The specific drug to add depends on the patient’s need. For example, if there is a compelling need to minimise hypoglycaemia, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, and thiazolidinediones are good choices. If there is a compelling need to promote weight loss, GLP-1 receptor agonists and SGLT-2 inhibitors are good choices. If cost is a major issue, sulfonylureas and thiazolidinediones are good choices. Insulin is of course an option if glycaemic control is not achieved otherwise.

The target HbA1c should be individualized to each patient, but a good target is 7%. If the target is not reached with the current treatment, the dose of the drugs should be increased or another drug should be added.

Drug class

Drug examples

Advantages

Disadvantages

Comments

Biguanides

Metformin

Long experience, Weight neutral

GI side effects, contraindicated in renal failure

First-line for all T2D

Sulfonylureas

Gliquidone, glipizide

Rapid effect, can be used in severe CKD

Risk of hypoglycaemia, weight gain, causes destruction of β-cells

Good second choice if cost is an issue

First choice in severe CKD

Thiazolidinediones

Pioglitazone

Improved lipid profile

Weight gain, increased risk of bladder cancer

Good second choice if cost or hypoglycaemia is an issue

GLP-1 receptor agonists/Incretin mimetics

Liraglutide, dulaglutide, semaglutide

Weight loss, reduction of CVD risk

GI side effects, administration by injection, expensive

First-line for all T2D with ASCVD, CKD, or HF.

Good second choice if weight loss or hypoglycaemia is an issue

DPP-4 inhibitors

Vildagliptin, sitagliptin

Weight neutral, no side effects

Expensive

Good second choice if hypoglycaemia is an issue

SGLT-2 inhibitors

Empagliflozin, dapagliflozin, canagliflozin

Weight loss, BP reduction, reduction of CVD risk

UTI, genital fungal infections, low bone density (fractures), increased risk of ulcer and amputation (canagliflozin)

First-line for all T2D with ASCVD, CKD, or HF.

Good second choice if weight loss or hypoglycaemia is an issue

(Me)glinides

Nateglinide, repaglinide

Rapid effect

Risk of hypoglycaemia, weight gain

Not much used

Alpha-glucosidase inhibitor

Acarbose

Weight neutral

GI side effects, frequent dosing, only decreases postprandial glucose

Not much used

Amylin analogues

Pramlintide

Weight loss

GI side effects, frequent dosing, injection, expensive

Not available in Europe yet

Other stuff

  • Diabetic patients have delayed wound healing, which might be evidenced after an operation
  • Dawn phenomenon refers to steadily rising blood glucose level during the night, resulting in morning hyperglycaemia
    • Due to high cortisol and GH levels during the night
    • Have hyperglycaemia during the night
    • It’s avoided by giving long-acting insulin before bed
  • Somogyi effect refers to morning hyperglycaemia due to too high long-actin insulin dose in the evening, which stimulates hormones which increase blood glucose during the night
    • Have hypoglycaemia during the night
    • It’s avoided by lowering the dose of long-acting insulin in the evening
  • The difference between human insulin and insulin analogues is that insulin analogues have some amino acids changed to change the rate of absorption
  • Insulin detemir, glargine, degludec are long-acting insulin analogues
  • NPH insulin is an intermediate-acting insulin
  • Regular insulin is the short-acting insulin
  • Insulin lispro, aspart, glulisin are rapid-acting (or ultra-short-acting) insulin analogues
  • Insulin resistance is measured by the HOMA index
    • HOMA index = fasting glucose * fasting insulin / 22,5
  • The thiazolidinediones and metformin are so-called insulin sensitizers
  • The normal daily insulin secretion is 0,5 – 0,6 units per kg of body weight
  • The “worst” type of insulin is premix insulin, a mix of short-acting and long-acting insulin
    • I don’t know why they consider it the “worst”, perhaps because it’s part of the less optimal insulin regimen
  • Insulin regimens for insulin-requiring diabetes
    • Intensive conservative insulin regimen
      • This is called basal-bolus regimen anywhere outside Hungary
      • = shorter acting insulin before the each of the 3 meals of the day, with longer acting insulin in the background
      • The recommended type of insulin regimen
      • Urban type
        • Urban people wake up later, so they have slightly different regimen
        • Short-acting insulin at 8, 12, 17
        • Intermediate-acting insulin at 21
      • Rural type
        • Urban people wake up earlier, so they have a slightly different regimen
        • Short-acting insulin at 6, 12, 18
        • Intermediate-acting insulin at 6, 22
      • Type with long-acting (basal) insulin
        • Short-acting or rapid-acting insulin at 8, 12, 17
        • Long-acting (basal) insulin once or twice a day
    • Once-daily or twice-daily regimen
      • = give premix insulin containing both short-acting and long-acting insulin once or twice a day, before breakfast and dinner
      • Not recommended for type 1 diabetes
        • May be used in patients refusing to take multiple insulin injections
      • May be use for type 2 diabetes patients who need insulin for glycaemic control
    • Insulin administered by pump
      • Insulin pumps administer tiny amounts of rapid-acting insulin continuously

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