Medwiki

Diabetes mellitus

What is it

Diabetes mellitus is a disease where there is dysregulation of the glucose transport pathways.

The 2 main ones are:

  • Diabetes type 1
  • Diabetes type 2

Some other types of diabetes are:

  • Secondary DM This is DM as a consequence of another disease, like pancreatitis or cystic fibrosis
  • Gestational DM This is generally type 2 diabetes during pregnancy
  • Impaired glucose tolerance This is an intermediate between normal and diabetes

Etymology

The term diabetes mellitus comes from greek, with diabetes coming from a word which meant siphon or pass through, describing one of the key symptoms of diabetes, polyuria.

Mellitus means sweet, which describes the sweet tasting urine from glucosuria. Contrast this with diabetes insipidus, which means lots of urine which is tasteless (insipid), as it is a endocrine disorder with reduced ADH action.

Lots of sweet urine is shared between type 1 and type 2.

T1DM

Type 2 diabetes mellitus (T2DM) Pathophysiology

Type 2 diabetes is simply, resistance to insulin. The process that leads to this is complex and will be covered.

NIDDM and IDDM

Type 2 diabetes is often found as non-insulin dependant diabetes, as we only see insulinopaenia in late stage T2DM. In NIDDM you still have beta islet function and will produce insulin, however is it often from resistance to this insulin that pathology arises. It is associated with obesity, lack of exercise, poor diate, or disease. (no shit) It may require insulin supplementation if it is severe, but once again your body can still produce it.

Chemical basis of T2DM

Diagnosis of T2DM

The symptoms of T2DM are the big 3, Polyuria, Polyphagia, and polydipsia, as well as the complications from the secondary effects.

Often a patient will come to you with a complaint related and you will then confirm and then test.

T2DM is confirmed with levels of HbA1C as well as fasting and postprandial plasma glucose levels.

If the HbA1C is between 42mmol/mol and 47 mmol/Mol you could say they have prediabetes, and HbA1C over 48mmol/Mol it is characteristic of T2D, consistent with chronic hyperglycaemia. No secondary test is required if HbA1c is over or equal to 53mmol/Mol

If fasting blood glucose is below 5.5mmol/L diabetes is unlikely. If it is 5.5-6.9mmol/L diabetes is possible and if it is over 7 diabetes is likely

HbA 1c

HbA1c is HAemoglobin which has been spontaneously glycated. It naturally happens but at a higher rate when there is hyperglycaemia. It is irreversible and will also stay around for the life of the RBC therefore giving a good measure of recent hyperglycaemic episodes.

Complications of T2DM

You get 3 things in T2DM

  • Hyperglycaemia
  • Hyperinsulinaemia
  • Insulin resistance

Hyperinsulinaemia & insulin resistance

Hyperinsulinaemia and insulin resistance go hand in hand:

As there is high blood glucose there is more insulin produced. As there is more insulin produced there is more resistance. As there is more resistance there is more produced and so on and so forth. verify

Hyperinsulinaemia and insulin resistance leads to hypercholesterolaemia, hyperlipidaemia, promotion of atherosclerosis, and hypertension.

Insulin leads to increased hepatic production of VLDLs Insulin resistance leads to reduced effeciacy of LPL leading to impaired storage of TAGs from the bloodstream Insulin resistance also leads to Adipocytes releasing more FFAs into the blood stream High insulin signals to the kidneys to retain sodium and water increasing blood volume and pressure. It also signals to the sympathetic nervous system to promote vasoconstriction.

and of course, hypertension, hyperlipidaemia and hypercholesterolaemia leads to atherosclerosis

Endothelial dysfunction

Hyperglycaemia

Clinical manifestations of these

The atherosclerosis and [results of hyperglycaemia] leads to a number of diseases namely:

  • Diabetic retinopathy
  • Hypertension
  • Heart disease
  • Kidney failure
  • PVD and diabetic neuropathies, which can lead to infection (diabetic foot ulcer)

Insulinopaenia

This is a lack of insulin in the body. This is ultimately the insulin endstage that we will see with many patients with type 2 diabetes (it is the primary cause of T1DM).

As someone develops this we will see the need to replace insulin with injected analogues. See Insulin analogues + insulin pump and CGM for full list of insulin types mechanisms and basal bolus therapy.

Treatment of T2DM

The treatment of T2DM really depends on a few factors, such as what type of T2DM you have, and then how far along it is. Usually the flow chart is like this:

flowchart TD
    A([**Diagnosis**]) --> B

    B[**Therapeutic Lifestyle Change**]:::green --> C

    C[**Oral Monotherapy — Metformin if HbA1c > 50 mmol/mol**
   ]:::blue --> D

    D[**Combination Therapy — Oral Drugs Only
     Add empagliflozin or vildagliptin or dulaglutide sc**]:::purple --> E

    E[**Combination Therapy — Oral Drugs with Insulin**]:::orange

    classDef green fill:#7ac142,color:#fff,stroke:#5a9e2f
    classDef blue fill:#4a90d9,color:#fff,stroke:#2e6da4
    classDef purple fill:#8e44ad,color:#fff,stroke:#6c3483
    classDef orange fill:#f39c12,color:#fff,stroke:#d68910

The aims of management

We want to achieve normal glycaemia in the short term to prevent symptoms of hyperglycaemia and avert hypoglycaemia. Long term we want to prevent micro and macrovascular symptoms

Lifestyle changes.

The majority of T2DM we see is from

Pharmcologicals

The oral first like therapy is metformin, otherwise SGLT2 inhibitors, DPP-4 inhibitors and GLP-1r agonists as well as sulphonylureas (avoid in obese patients) when an alternative is needed. Additionally SGLT2 and DPP-4 inhibitor are recommended when there is a cardiovascular risk’

See Hypoglycaemics for in depth details

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