When regulation fails: diabetes

When blood glucose regulation fails, glucose builds up in the blood. This is diabetes — one symptom for two very different diseases.

Two diseases, two mechanisms

                    TYPE 1                    TYPE 2
------------------  ----------------------    ----------------------
mechanism           β cells are DESTROYED     cells no longer RESPOND
                    (autoimmune disease)      to insulin (resistance)
insulin present?    NO, none at all           YES, often in excess
age at onset        often childhood           often after 40
share of cases      ~ 10 %                    ~ 90 %
factors             genetic, trigger          overweight, inactivity,
                    poorly understood         heredity
treatment           insulin MANDATORY         exercise, diet, drugs,
                    for life                  sometimes insulin

Type 1 is an autoimmune disease: the immune system destroys the pancreatic β cells, taking them for non-self. It results from no behaviour and cannot be prevented.

Type 2 is a loss of sensitivity: insulin is there, often in large amounts, but cells no longer respond. The pancreas compensates by producing more, until it exhausts itself.

The warning signs

intense thirst and copious urine   excess glucose is filtered by the kidney
                                   and drags water with it
fatigue                            glucose does not enter the cells
weight loss (type 1)               the body burns fat and muscle

These three signs express the same thing: glucose in abundance in the blood, and cells with no access to it.

Diagnosis

   fasting blood glucose  <  1.10 g/L    normal
                          1.10 - 1.25    prediabetes
                          ≥  1.26 g/L    DIABETES (confirmed by a second test)

Type 2 develops for a long time without symptoms: an estimated one case in five goes undiagnosed. Yet vascular damage begins before symptoms, which justifies systematic screening after 45 or with risk factors.

Complications

They all stem from the same mechanism: excess glucose attaches to proteins and damages vessel walls.

   EYES      retinopathy -> leading cause of adult blindness
   KIDNEYS   nephropathy -> leading cause of dialysis
   NERVES    neuropathy  -> loss of sensation, unnoticed wounds
   HEART     heart attack, stroke: risk multiplied by 2 to 4

These complications set in over ten to twenty years and are largely avoidable with good glucose control — hence the importance of monitoring, measured by glycated haemoglobin, which reflects the average of the last three months.

Treatment, and the story of a discovery

Before 1921, type 1 diabetes was a death sentence in children, with survival measured in months. Banting and Best isolated insulin that year; the first patient treated, aged 14, survived. The patent was sold for a symbolic dollar, its authors judging it should belong to no one.

Today insulin is produced by genetically modified bacteria carrying the human gene — a direct application of the universality of the genetic code.

A word on thermoregulation

The same scheme applies to temperature:

   too HOT   ->  sweating, vasodilation      ->  cooling
   too COLD  ->  shivering, vasoconstriction ->  warming

Sensor (skin and hypothalamus), controller (hypothalamus), effectors (sweat glands, muscles, vessels): the structure is identical. One regulation loop, two applications — that is what makes the model so powerful.

Summary

• Type 1 destroys the β cells (autoimmune): no insulin at all, ~10 % of cases.
• Type 2 is insulin resistance: it is present but ineffective, ~90 % of cases.
• Diagnosis: fasting glucose ≥ 1.26 g/L, confirmed.
• Type 2 runs for a long time without symptoms, hence screening.
• Complications: eyes, kidneys, nerves, heart — all vascular in origin.
• Thermoregulation follows exactly the same sensor-controller-effector scheme.