Diabetes Mellitus: aetiology and strategies

Type 1 Diabetes Mellitus

• Accounts for 8% of all diabetes cases
• Risk factors
  • • Genetics – 50% risk in identical twins, 6% risk in sibling, 5% risk if parent affected
    • Diet, vitamin D deficiency, obesity, viral infections
• Associated with other autoimmune disorders
  • • Especially thyroid disease (Graves or Hashimotos) in 22%, also pernicious anaemia, coeliacs, vitiligo, Addison’s.
    • Check TFTs and coeliac antibodies routinely in all type 1 diabetics
• Reduces life expectancy by around 12 years on average
• Onset
  • • Peaks from 6 months old to 5 years, and then again in puberty
    • 30% occurs in adulthood (suspect especially if there is autoimmunity and a lean patient)
    • If not clear-cut diagnosis, check autoantibodies (see diagnosing diabetes)
• General management
  • • Individualised care plan
    • Similar lifestyle advice as T2DM
    • DAFNE – a course to help T1DM adjust their insulin according to diet
• DAFNE / dietary advice
  • • Carb counting involves dividing carbohydrates consumed by a patient specific ratio to calculate the units insulin required
    • Can use the Carbs and cals app
    • Every 10g carbs is one Carbohydrate Portion (CP) – so if 1:1 ratio, 40g carbs = 4 CPs = 4 units of insulin.
    • Sometimes 1:10 ratio quoted instead (ie 10g of carbs for every unit of insulin) – this is the starting ratio for most type one diabetics
    • Examples of carbohydrate content / portion
      • • 1 medium slice of bread 15g
        • A panini 50g
        • A jacket potato 50g
        • A banana 25g
        • An apple 15
        • Cooked pasta is 1/3 of it’s weight (so 150g is 50g carbs)
        • I pint milk 30g
    • Fat and protein also effect sugar levels – ratios: carbs 1:10, protein 1:40, fat 1:30.
    • Carb counting takes time… usually not taught as an inpatient
    • Ensure diabetics get the right nutritional supplements in hospital if required (eg Fresubin protein energy, not the 2 kcal fresubin or energy fresubin which can cause high sugars (and are more usually used in malnutrition)
    • Do not advise low glycaemic index diet for glucose control
• Exercise advice
  • • A long acting insulin like Levemir is probably best for very active type 1 diabetics who exercise a lot
    • A patient can change their insulin ratio depending on when they exercise
    • Don’t exercise if CBGs outside 7 – 15 (and if 4-6.9, delay and eat)
    • Exercising after 4pm increases the risk of going hypoglycaemic overnight
    • Patients should always take hypo-treatment with them when exercising
    • Take complex carbs up to 2 hours before exercise and simple carbs within 2 hours.
• Targets
  • • Usually target HbA1c of <48
    • If CKD (not on dialysis) – aim <48 to <64, depends on the person
    • Check HbA1c every 3-6 months
    • Target CBGs 5-7 before breakfast, 4-7 before other meals and 5-9 before bed
    • For time in range (TIR) targets – see diabetes tech
• Offer Continuous Glucose Monitoring (CGM, either real-time or scanned)
  • • Patients still need to check occasional CBGs to check accuracy of sensor (and as back up)
    • See diabetes tech
• If checking fingerprick CBGs
  • • Advise to check at least 4 x day
    • Check up to 10 times daily if poor control, planning pregnancy/pregnant, exercising a lot, unwell, impaired hypoglycaemic awareness, driving long distance
• Medications in type 1 DM 
  • • Metformin can be given to T1DM with BMI > 25
    • SGLT2is are contraindicated
    • Statins offered to all type 1 diabetics aged >40
    • ACE-I / ARB given if CKD, albuminuria or hypertension
• Basal-bolus regime
  • • Rapid/short acting before meals (not after) + once or twice daily intermediate/long acting insulin
    • Offers good flexibility for glucose control
    • Get basal dose right first, then adjust short-acting
    • If long-acting insulin needs increasing – go up by 2 units
    • If you don’t know the dose of basal insulin in a diabetic patient being admitted, just give 10 units of lantus and figure it out later
    • See insulin for more detail
• Mixed / biphasic
  • • Once to three times daily doses of combination insulin
    • Not advised for newly diagnosed T1DM
    • Sometimes used if basal bolus regime not possible
• Consider pump therapy / closed loops
  • • Gives regular short acting insulin, no need for long acting
    • More expensive, but closely matches insulin requirements to individual
    • Recommended if disabling hypoglycaemia when trying to achieve HbA1c target, or HbA1c >69 despite a high level of care
    • See diabetes tech

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Type 2 Diabetes

• 90% of diabetes cases. Affects more than 5 million adults in the UK, and 20% of hospital inpatients
• > 100 children diagnosed with type 2 DM every year in the UK
• Higher prevalence in ethnic minorities (especially those from the Indian subcontinent)
• Around one million people in the UK with T2DM are undiagnosed
• Decline in beta cell function is already advanced at time of diagnosis (begins around a decade before – ‘pre-diabetes’)
• Life expectancy in type 2 DM is reduced by around 10 years (deprivation adjusted standardised mortality rate in T2DM is around 1.5)
• Multifactorial aetiology
  • • Not just due to reduced insulin sensitivity
    • Increased glucagon secretion, lipolysis, glucose reabsorption and hepatic glucose production (esp overnight, so higher sugars in the morning)
    • Decreased glucose uptake, insulin secretion, incretin effect
    • Impaired appetite regulation
• Risk factors
  • • Obesity – accounts for around 80% of the risk
    • Family history – 4x greater risk. 15% risk if one parent has T2DM, 75% if both
    • Ethnicity – 3x greater risk if Asian, African/Afro-Caribbean
    • History of gestational DM – 7 x increased risk
    • High glycaemic index diet (independent of weight gain)
    • Medications
    • Polyendocrine metabolic ovarian syndrome (PMOS)
    • If born before 35 weeks gestation
• Prevention – weight loss and lifestyle modification best
  • • Weight loss of 15kg in DM over 12 months equates to an 86% chance of remission, 10-15kg = 57% chance, 5-10kg = 34% chance and 0-5kg = 7% chance
    • Recommended diet: high fibre, low glycaemic index carbs, low fat, oily fish
    • Avoid high salt and high glycaemic index carbs
    • Regular exercise
• HbA1c Targets
  • • Target 48-58 for most – eg if micoalbuminuria, age <40 or duration of DM < 10 years
    • Target HbA1c of 48 if diet-controlled or on single drugs not associated with hypoglycaemia (like metformin)
    • Target HbA1c 53 if on sulphonylurea
    • Target 58-62 if CKD stage 3 or 4, or albuminuria
    • Target 58-68 if CKD stage 5 or on dialysis
    • If HbA1c > 58 – consider escalating treatment (but also check adherence)
    • Consider higher HbA1c targets if person at risk of falls, impaired hypoglycaemic awareness, drivers, reduced life expectancy
• Monitoring
  • • Self-monitoring CBGs is not routine, but should be used if on insulin or sulfonylurea, previous hypoglycaemia, pregnant
    • Continuous Glucose Monitoring used in T2DM if on insulin and any of:
      • • Recurrent hypos
        • Impaired hypo awareness
        • Certain disabilities
        • Would otherwise require checking CBGs >8x day
        • Would otherwise need a carer to monitor CBGs
    • A 1% reduction in HbA1c is associated with a 14% reduction in MI, 37% reduction in microvascular complications and a 21% reduced risk of DM-related death
• Drugs in T2DM – see diabetes medications and glucose control
• If starting insulin in T2DM
  • • 1^st line is NPH (neutral protamine Hagedorn) – once or twice daily
    • NPH + short acting (separate or premixed) – if HbA1c >75
    • Consider determir or glargine as alternative to NPH (sometimes easier). Switch to one of these from NPH if there’s hypoglycaemia

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Other forms of diabetes mellitus

• MODY (maturity onset diabetes of the young) / monogenic DM
  • • Often a young, lean person with mild hyperglycaemia and a strong family history of diabetes diagnosed at a young age. More common in women.
    • Do genetic testing
    • No autoimmune markers
    • Exquisitely sensitive to sulphonylureas and often maintain excellent glycaemic control for years on these medications. May not need insulin.
    • Prevalence of 3 antibodies is <1% (can help discriminate)
• LADA (latent autoimmune diabetes in adults)
  • • Suspect  (LADA) in a middle aged, lean patient with hyperglycaemia
    • Shares traits of T1DM and T2DM. Behaves like an insidious presentation of T1
    • Often have autoantibodies especially GAD65
    • C peptide often low and are often used to guide treatment strategies
• Ketosis-prone DM
  • • More common in an overweight, non-white patient with DKA (and especially common in black men)
    • Often insulin can be discontinued after a few months
• Haemochromatosis – an uncommon cause of diabetes. Look for other features. More here
• Pancreatic (type 3c)
  • • Underdiagnosed, could represent 8% of DM
    • Consider CT pancreas if older, losing weight and appears to be T1DM
    • Causes
      • • Acute pancreatitis
        • Chronic pancreatitis
        • Carcinoma
        • Haemochromatosis
        • Cystic fibrosis
        • Surgery
• Gestational diabetes – more here
• MIDD (Maternally inherited DM and deafness) – mitochondrial inheritance
• Drug-induced
  • • Steroids – more here
    • Betablockers, diuretics (high dose thiazides), statins, oral contraceptive – all cause small increases in blood sugar
    • Antipsychotics (especially clozapine, olanzapine and quetiapine)
    • Antiretrovirals
    • Post-transplant drugs
    • Tyrosine kinase inhibitors
    • Interferon alpha
• Endocrine
  • • Cushing’s syndrome
    • Acromegaly
    • Glucagonoma, somatostatinoma
    • Hyperthyroidism
    • Phaeochomocytoma

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Diabetes education

• Adherence to medications and insulin (and entitlement to free prescriptions)
• Sick day rules
  • • Stop ACE-I, ARBs, NSAIDs due to risk of AKI
    • Stop metformin if risk of dehydration
    • Stop SGLT-2 inhibitors (and check ketones)
    • Stop GLP-1 receptor agonists if risk of dehydration
    • Increase CBG monitoring
    • Adjust insulin
    • For type 1DM – never omit insulin entirely, check CBGs more frequently including though the night, check ketones
• Hypo avoidance (consider medic alert especially for type 1)
• DVLA advice (more here)
• Pregnancy / planning pregnancy (more here)
• Monitoring – HbA1c every 3-6 months in type 2 until stable, then every 6-12
• Diet, exercise, weight loss, smoking
• DAFNE (type 1), DESMOND (type 2)
• Fasting – avoid in T1DM, especially if poorly controlled

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Diabetes clinic – screening and assessment

• Glycaemic control – HbA1c / time in range, medications/adherence, monitoring, injection sites, current treatment
• CV risk – Blood pressure, lipids, smoking, CV risk (if high, SGLT2 inhibitors particularly useful)
• Kidneys – Serum creatinine and Urine ACR (annually after diagnosis in T2DM, and more frequently if sharp decline, and annually after 5 years from diagnosis in T1DM) – often not monitored enough
• Feet
• Retinal screen
• BMI and diet
• Immunisations – flu, pneumococcus, covid