18.7 — Diabetes

Type 2 diabetes was, until recently, described as a progressive incurable condition that could only be managed.

It can be put into remission. Around 46 percent of people achieved remission at one year in the DiRECT trial, using a structured low-calorie diet delivered in ordinary general practice — normal blood glucose, off all medication.

That is the most hopeful fact in this Part, and it is still not widely known.

Chapter 12.5 covered the physiology. This chapter is what to do about it.

The types, briefly

Type 1 — autoimmune destruction of beta cells. Around 5 to 10 percent. Requires insulin, always.

Type 2 — insulin resistance plus progressive beta cell failure. Around 90 percent.

And type 2 is not "mild diabetes". It causes the same complications, and because it is silent for years it is frequently more advanced at diagnosis.

Gestational (Chapter 15.6). MODY — single-gene, frequently misdiagnosed, and sometimes needing no treatment or responding to low-dose sulfonylureas (Chapter 12.5).

And adult-onset type 1 is regularly misdiagnosed as type 2, particularly in people who are not overweight. Antibody testing and C-peptide measurement distinguish them (Chapter 2.3), and the distinction matters because the treatment differs entirely.

Diagnosis

Test	Diabetes	Prediabetes
Fasting glucose	≥7.0 mmol/L	6.1–6.9
HbA1c	≥48 mmol/mol	42–47
2-hour glucose tolerance	≥11.1 mmol/L	7.8–11.0

Two abnormal results, or one plus symptoms.

Symptoms of hyperglycaemia: excessive thirst, excessive urination, weight loss, fatigue, blurred vision, recurrent infections, and slow-healing wounds.

And the mechanism of the first two is Chapter 10.2: glucose above the renal threshold spills into the urine and drags water with it osmotically.

Prediabetes matters. Around 5 to 10 percent per year progress to diabetes — and structured lifestyle programmes reduce that by around 58 percent, which outperformed metformin in the Diabetes Prevention Program. It is a genuine window.

Why control matters

Because the complications are what diabetes actually is.

Microvascular — damage to small vessels, driven mainly by glucose:

Retinopathy — a leading cause of blindness in working-age adults, and largely preventable. Annual retinal screening detects it before vision is affected, when laser or injections preserve sight (Chapter 11.11).

Nephropathy — and the earliest marker is albumin in the urine (Chapter 10.1). Detecting it at that stage and starting an ACE inhibitor genuinely changes the long-term outcome.

Neuropathy — glove-and-stocking numbness (Chapter 11.8), and autonomic neuropathy causing gastroparesis, postural hypotension, erectile dysfunction and — dangerously — silent ischaemia (Chapter 11.9).

Macrovascular — accelerated atherosclerosis:

Heart attack, stroke and peripheral arterial disease. Cardiovascular disease is the leading cause of death in type 2 diabetes, and it is driven by blood pressure and lipids at least as much as by glucose.

Which is the key insight of modern diabetes care: treating glucose alone is not enough.

The foot — where neuropathy, poor circulation and impaired healing combine (Chapter 14.4).

And the prevention is inspection. Daily foot checks, well-fitting shoes, never walking barefoot, and annual screening with a monofilament prevent a large proportion of amputations.

Treatment of type 2

And the landscape has changed substantially.

Lifestyle first, and it is treatment rather than preamble.

Weight loss is the most effective intervention available. Around 15 kg produces remission in a substantial proportion, and the likelihood is highest with shorter disease duration.

Physical activity improves insulin sensitivity directly, independent of weight.

Diet. And the honest position: several patterns work — Mediterranean, low carbohydrate, low calorie — and adherence matters more than which one. The best diet is the one a person will actually follow.

Metformin — first-line, cheap, effective, weight-neutral, and it has been in use since the 1950s. Derived from a compound in French lilac (Chapter 3.7). Gastrointestinal side effects are common initially and reduced by slow titration and modified-release preparations. It lowers B12 over years, which is worth checking.

And then two classes that have changed the field.

SGLT2 inhibitors — blocking glucose reabsorption in the kidney so it is lost in the urine (Chapter 1.4).

And their benefits go well beyond glucose. They reduce cardiovascular death, hospitalisation for heart failure, and progression of kidney disease — in people with and without diabetes. They are now used as heart failure and kidney drugs in their own right (Chapters 18.4, 10.6).

Their specific risks: genital fungal infections, and euglycaemic diabetic ketoacidosis — ketoacidosis with a near-normal glucose, which is easily missed and is a reason to stop them during acute illness or before surgery.

GLP-1 receptor agonists — mimicking the gut hormone (Chapter 12.7).

They lower glucose only when it is high, so they do not cause hypoglycaemia; they slow gastric emptying; and they reduce appetite centrally.

Weight loss of 10 to 20 percent, plus reduced cardiovascular events. Nausea is the main side effect and usually settles.

Together, these two classes shifted diabetes treatment from "lower the number" to "reduce the outcomes that matter", and guidelines now recommend them based on cardiovascular and kidney risk rather than on glucose alone.

Other agents: sulfonylureas (effective, cheap, cause hypoglycaemia and weight gain), DPP-4 inhibitors, pioglitazone, and insulin when beta cell function has declined sufficiently.

Bariatric surgery — produces remission in a majority, and glucose improves within days, before meaningful weight loss (Chapter 12.5), which points to gut hormone changes as the mechanism.

Treatment of type 1

Insulin, and the improvements have been in delivery.

Basal-bolus regimens — long-acting insulin plus rapid-acting with meals.

Pumps — continuous subcutaneous infusion.

Continuous glucose monitoring — a sensor reading interstitial glucose every few minutes, with alarms.

And closed-loop systems — the monitor and pump communicating and adjusting automatically. These have made a substantial difference to both control and to the mental burden, which is considerable and frequently underestimated.

Carbohydrate counting and structured education programmes improve outcomes measurably.

Targets

HbA1c targets are individualised, and this matters.

Around 48 to 53 mmol/mol for most.

Relaxed in the frail elderly, in those with hypoglycaemia unawareness, and in limited life expectancy — because tight control in an 85-year-old causes hypoglycaemia, falls and confusion without delivering benefits that take a decade to appear.

Overtreatment of older people with diabetes is a recognised and correctable harm.

Time in range — from continuous monitoring — is increasingly used alongside HbA1c, and it captures what an average hides (Chapter 12.5).

And blood pressure and lipids are targeted at least as vigorously as glucose, because that is where the cardiovascular benefit comes from.

The emergencies

Hypoglycaemia — Chapter 12.5, and the practical version is in Chapter 23.11.

Diabetic ketoacidosis — mainly type 1.

No insulin means fat breakdown runs unchecked, ketones accumulate, and the blood becomes acidic (Chapter 1.6).

Vomiting, abdominal pain, deep sighing breathing — Kussmaul respiration, blowing off carbon dioxide to compensate (Chapter 10.4) — a sweet acetone smell on the breath, dehydration and drowsiness.

Treatment: fluids first, then insulin, with careful potassium replacement — because insulin drives potassium into cells and the level falls precipitously (Chapter 10.3).

And the sick day rules are what prevent it: never stop insulin during illness, even if not eating; check glucose and ketones more often; drink plenty; and seek help if ketones are high or vomiting prevents fluids.

Hyperosmolar hyperglycaemic state — mainly type 2, in older people. Very high glucose, profound dehydration, and little ketosis because some insulin remains. Mortality is higher than DKA, and it develops over days rather than hours.

Living well with it

Structured education programmes improve outcomes and are under-attended.

Annual checks: HbA1c, blood pressure, lipids, kidney function and urine albumin, retinal screening, foot examination, and weight.

Vaccination — influenza and pneumococcal.

Sick day rules for both insulin and for the drugs that need stopping during dehydrating illness — ACE inhibitors, ARBs, diuretics, metformin and SGLT2 inhibitors (Chapter 10.6).

Driving rules apply for insulin and sulfonylurea users, with specific requirements for checking glucose before and during driving.

And the psychological burden is real and measurable. "Diabetes distress" affects a substantial proportion, and depression is around twice as common as in the general population. It affects self-management directly, and it is treatable.

What is genuinely improving

Remission is achievable in type 2 — the headline of this chapter.

Complication rates have fallen substantially in countries with good screening and risk factor management. Rates of amputation, blindness and end-stage kidney disease attributable to diabetes have declined markedly over recent decades.

Closed-loop insulin delivery has changed daily life for type 1.

Drugs that reduce cardiovascular and kidney events rather than just glucose.

And immunotherapy delaying type 1 — an antibody that delays the onset of clinical disease in high-risk relatives by around two years is now approved, the first treatment to alter the disease process rather than replace the missing hormone.

Diabetes remains a serious condition that shortens life. It is also, now, one where the trajectory can be substantially changed — and in its commonest form, sometimes reversed.

What the next page fixes

Chapter 18.8 covers the condition underlying most type 2 diabetes, and the one where medicine has most consistently misunderstood both the biology and the people affected.