Type 1 diabetes

• is typically considered a disease of children and the young
• but the majority of people with type 1 diabetes are adults, and as many as 42% of type 1 diabetes cases have their onset in people between 30 and 60 years of age
• Consider if there are no other feature of the metabolic syndrome and there is presence of
  • ketonuria (which may be absent)
  • polyuria
  • polydipsia
  • weight loss or BMI <25 kg/m2
  • young age
  • family history of autoimmune disease
  • rapid onset of symptoms. 
• 90% of patients with type 1 diabetes test
  • positive for
    • glutamic acid decarboxylase (GAD) and/or 
    • insulinoma antigen 2 (IA-2) antibodies 
  • low C-peptide levels
    • measure of pancreatic beta cell function. 
    • Is co-secreted (equimolar amounts) with insulin from pancreatic beta cells 
    • measure of insulin secretion.
    • The degradation rate of c-peptide (half life 30mins) in the body is slower than that of insulin (3–5 min) therefore more stable test window of fluctuating beta cell response. And negligible hepatic clearance. cleared in the peripheral circulation at a constant rate
    • c-peptide in the fasting state is 0.3–0.6 nmol/l, postprandial is 1–3 nmol/l
    • Diagnosis:
      • type 1 diabetes mellitus (T1DM) – c-peptide level of less than 0.2 nmol/l  (on non-fasting sampling support the diagnosis of type 1 diabetes)
      • endogenous hyperinsulinism – Inappropriately high levels of insulin and C-peptide during hypoglycaemia
      • exogenous hyperinsulinism – Inappropriately high levels of insulin with low C-peptide
    • C-peptide level may correlate with microvascular and macrovascular complications and future use of insulin therapy, as well as likely response to other individual therapies. 

Type 2 DM: can occur in children + adolescents if overweight but usually older adults, often family hx. Most people are asymptomatic.

Latent Autoimmune Diabetes of Adults (LADA): 

• Called type 1.5
• Latent autoimmune diabetes with ß-islet cell antibodies that occurs more commonly in adulthood. 
• often presents similarly to type 2 diabetes, but it involves a
  • more rapid course of ß-cell destruction
  • poorer metabolic response to non-insulin therapy
  • more rapid progression to requiring insulin to control hyperglycaemia due to ß-cell failure
• requires rx w insulin within a relatively short period after dx (often next 2yrs). 
• Tend to be in young (30-40yr) people who have a personal and/or family hx of autoimmune diseases. 
• Testing with GAD (glutamic acid decarboxylast) antibodies can confirm the dx + prompt counselling about likely developing of other autoimmune disease.

Monogenic diabetes

• Monogenic diabetes is a collection of single-gene mutation disorders that account for1–2% of diabetes cases. 
• Cases usually develop before 25 years of age and are often non-insulin requiring. 
• Monogenic diabetes can be misdiagnosed as either type 1 or type 2 diabetes.
• Monogenic diabetes is genetically heterogeneous, but all forms are dominantly inherited, unless they occur as a result of a de novo mutation. 
• 2 forms:
  • Neonatal diabetes mellitus, occurring in the first six months of life (rare)
  • Maturity onset diabetes of the young (MODY)
• MODY 
  • may vary in the severity of hyperglycaemia. 
  • The most prevalent subtypes are due to mutations in the genes HNF1A, GCK and HNF4A. 
  • Suspected cases should be referred to a specialist endocrinologist, and management options and possible genetic diagnosis should be considered

Gestational diabetes mellitus:

• defined as carbohydrate intolerance that begins or is first diagnosed during pregnancy. In most women, GDM is asymptomatic.
• Risk factors for GDM
  • Previous GDM
  • Previously elevated blood glucose level
  • Ethnicity: south and southeast Asian, Aboriginal, Pacific Islander, Maori, Middle Eastern, non-Caucasian African
  • Age ≥40 years
  • Family history of diabetes mellitus (first degree relative with diabetes mellitus or a sister with GDM)
  • Obesity, especially BMI >35 kg/m2
  • Previous macrosomia (baby with birth weight >4 500 g or >90th percentile) 
  • Polycystic ovarian syndrome
  • Medications: corticosteroids, antipsychotics
• Screening and diagnosis of GDM
• All pregnant women should be screened between 26 and 28 weeks gestation with a non-fasting glucose challenge
• Women whose levels are ≥7.8 mmol/L should have a formal (fasting) 75 g OGTT
• The diagnosis of GDM is made on the basis of a 75 g OGTT where the fasting level is >5.5 mmol/L or 2 hour result is ≥8.0 mmol/L
• A population-based study reported the incidence of type 2 diabetes in women with previous GDM was 3.7% at 9 months postpartum, 13.1% at 5 years postpartum and 18.9% 9 years postpartum (versus 2% in controls without GDM)

Medication induced diabetes: commonly prednisolone + olanzapine that may require hypoglycaemics, once med withdrawn need for treatment may change but pt’s should still be considered to have DM & require ongoing CVD monitoring.

Other causes

1. Diseases of the exocrine pancreas: Any process that diffusely injures the pancreas can cause diabetes. With the exception of that caused by cancer, damage to the pancreas must be extensive for diabetes to occur, If extensive enough, cystic fibrosis and hemochromatosis will also damage β-cells and impair insulin secretion
   1. Pancreatitis
   2.  Trauma/pancreatectomy
   3. Neoplasia
   4. Cystic fibrosis
   5. Hemochromatosis
   6. Fibrocalculous pancreatopathy
2. Others Endocrinopathies = Several hormones (e.g., growth hormone, cortisol, glucagon, epinephrine) antagonize insulin action. Excess amounts of these hormones (e.g., acromegaly, Cushing’s syndrome, glucagonoma, pheochromocytoma, respectively) can cause diabetes. This generally occurs in individuals with preexisting defects in insulin secretion, and hyperglycemia typically resolves when the hormone excess is resolved
   1. Acromegaly
   2. Cushing’s syndrome
   3. Glucagonoma
   4. Pheochromocytoma
   5. Hyperthyroidism
   6. Somatostatinoma
   7. Aldosteronoma
3. Drug- or chemical-induced = Many drugs can impair insulin secretion. These drugs may not cause diabetes by themselves, but they may precipitate diabetes in individuals with insulin resistance.
   1. Nicotinic acid
   2. Glucocorticoids
   3. Thyroid hormone
   4. β-adrenergic agonists
   5. Thiazides
   6. Dilantin
   7. Interferon 
4. Infections
   1. Congenital rubella
   2.  Cytomegalovirus
5. Other genetic syndromes sometimes associated with diabetes
   1. Down’s syndrome
   2. Klinefelter’s syndrome
   3. Turner’s syndrome

Complications in early-onset type 2 diabetes compared with older-onset type 2 diabetes

• Lifetime risk of complications greater with onset at a younger age
• Life expectancy reduced
• Non-alcoholic fatty liver disease is twice as common
• Earlier onset of microalbuminuria and end-stage renal failure
• Earlier onset and greater prevalence of diabetic retinopathy
• Earlier onset of neuropathy
• Apolipoprotein B concentration is higher despite statin therapy
• Risk of myocardial infarction is 14 times higher compared with age cohort, while older-onset type 2 diabetes risk is 2–4 times higher
• Early-onset of diastolic myocardial dysfunction
• Reduced fertility, and greater pregnancy complications
• Risk of premature decline in cognitive function
• Higher rate of diabetes-related psychological distress and psychological issues, especially depression
• Limited work capacity and consequent socioeconomic impact
• Reduced quality of life

History: 

Clinical symptoms suggestive of diabetes

Symptoms of diabetes include:

• lethargy, polyuria, polydipsia
• frequent fungal or bacterial infections
• blurred vision
• loss of sensation (ie touch, vibration, cold)
• poor wound healing
• weight loss.

1. Symptoms
   1. Hypoglycaemic
   2. Hyperglycaemic:
      1. polyuria, polydipsia, polyphagia, weight loss, nocturia
   3. Sequelae of hyperglycaemia and complications of diabetes:
      1. malaise/fatigue
      2. neurological and autonomic symptoms
      3. altered vision
      4. bladder and sexual dysfunction
      5. foot and toe numbness and pain
      6. recurrent infections (especially urinary and skin with delayed wound healing)
      7. gastrointestinal dysfunction (such as gastroparesis and nausea)
      8. poor dental hygiene and gingivitis
2. Predisposing factors
   1. Pancreatic disease, Cushing’s disease, obstructive sleep apnoea
   2. Medications (eg corticosteroids, antipsychotics; refer below)
   3. Autoimmune diseases (eg hypothyroidism or hyperthyroidism)
3. Medical history
   1. Gestational diabetes
   2. Other secondary causes (eg pancreatic disease) 
   3. Multimorbidities
      1. Overweight and obesity
      2. Hypertension
      3. Hyperlipidaemia
      4. CVD
   4. Specialist care
      1. Current or past surgical history
   5. Complications
      1. Eye 
   6. Complications
      1. Kidney
      2. Feet – discuss appropriate footwear, etc
      3. Other
4. Family history
   1. Haemochromatosis 
   2. Gestational diabetes
5. Psychosocial history
   1. Lifestyle
      1. Physical activity
      2. Smoking
      3. Diet
   2. Emotional and mental health
      1. Health literacy
      2. Social support network
6. Medications
   1. Past and current medications
   2. Complementary therapies
   3. Other therapy, glucose monitoring and technology
      1. Role of routine and non-routine SMBG
      2. Use of technology
7. Immunisations
   1. Influenza
   2. Pneumococcal
   3. Tetanus
8. Pregnancy and contraception
   1. Pregnancy planning
   2. Contraceptive use
9. Other
   1. NDSS enrolment and services
   2. Driving (interval depends on Assessing fitness to drive guidelines)
   3. Occupational factors
   4. Diving

Examination

Clinical signs of insulin resistance

1. Acanthosis nigricans – typically characterised by hyperpigmentation (darkening of skin pigment) and usually accompanied by a velvety change in texture of the affected skin. Common sites are the neck and axillae.
2. Skin tags – benign (non-cancerous) skin growths on the body or face. They can be smooth or wrinkled, skin-coloured or just slightly darker than skin colour and can vary in size.
3. Central obesity – defined by a high waist-to-hip ratio, waist-to-thigh ratio and waist circumference.
4. Hirsutism – excess facial and body hair, particularly on women

1. General
   1. BMI
   2. Waist circumference (cm)
   3. Blood pressure
   4. Central and peripheral vascular systems
2. Absolute CVD risk assessment (this may require calculation and investigations)
3. Complications of diabetes
   1. Feet  – sensation and circulation, skin condition, pressure areas, interdigital problems, abnormal bone architecture
   2. Peripheral nerves – tendon reflexes, sensation (touch [eg 10 g monofilament] and vibration [eg 128 Hz tuning fork]), existence of peripheral neuropathic changes
   3. Heart – ECG for symptomatic disease or dysrhythmia
   4. Sexual dysfunction – both male and female sexual dysfunction
   5. Eyes – acuity, retinopathy
   6. Skin – for example, lipohypertrophy or dystrophy, acanthosis nigricans, mycotic infections
4. Psychological
   1. Depressive symptoms
   2. Diabetes distress
      1. Problem Areas in Diabetes (PAID)
      2. Diabetes Distress Scale (DDS)