Type 2 diabetes in adults
Differentials
Non-diabetic hyperglycaemia (pre-diabetes)
SIGNS / SYMPTOMS
People with non-diabetic hyperglycaemia (NDH) often have no specific differentiating signs or symptoms as both NDH and type 2 diabetes are generally asymptomatic.
INVESTIGATIONS
NDH is defined as raised blood glucose levels (HbA1c 42 to 47 mmol/mol [6.0% to 6.4%]; or fasting glucose 5.5 to 6.9 mmol/L [99.0 to 124.2 mg/dL]) that are not in the diabetes range but are associated with an increased risk of developing type 2 diabetes.[44]
Diabetes mellitus, type 1
SIGNS / SYMPTOMS
Tends to present in childhood or adolescence with the highest incidence observed in children aged 10 to 14 years, but can occur at any age.[89]
Adults with type 1 diabetes typically present with hyperglycaemia and usually (but not always) one or more of: ketosis; rapid weight loss; age <50 years; BMI <25 kg/m², personal and/or family history of autoimmune disease.[74]
INVESTIGATIONS
Urine ketones are often present in type 1 diabetes, but may be positive in type 2 diabetes if there is severe volume depletion.
Low (<0.2 nanomol/L) or absent C-peptide level.
One or more auto-antibodies (antiglutamic acid decarboxylase [GAD] antibodies, islet cell antibodies [ICA], insulin auto-antibodies, auto-antibodies to the tyrosine phosphates IA-2 and IA-2beta) are present in 85% of people with type 1 at the time of diagnosis, but may disappear within a few years.[75] Type 1 diabetes is defined by the presence of one or more of these autoimmune markers.
Glucose screening criteria cannot be used to differentiate type 1 and type 2 diabetes, as they are identical.
Latent autoimmune diabetes in adults (LADA)
SIGNS / SYMPTOMS
Typical age of onset of diabetes is over 30 years old. Patients are usually non-obese and respond initially to lifestyle modifications and oral agents. Production of insulin gradually decreases (between 6 months and 5 years), such that treatment with insulin is required.[90]
LADA is considered a subset of type 1 diabetes; however, people with LADA are frequently misclassified as having type 2 diabetes.
INVESTIGATIONS
Positive for at least 1 of the 4 antibodies commonly found in people with type 1 diabetes (ICAs and auto-antibodies to GAD65, IA-2, and insulin).[91]
Monogenic diabetes
SIGNS / SYMPTOMS
The two main forms of monogenic diabetes are maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM).
MODY affects 1% to 2% of people with diabetes.[92]
MODY is caused by mutation of a single gene (i.e., monogenic). As of 2020, at least 14 forms of MODY are known.[93]
It has autosomal dominant inheritance but de novo mutations have been reported.[93] It should be suspected in cases of diabetes in non-obese, young patients (adolescence or young adult) with family history of diabetes in two or more successive generations.[94]
Patients are often misclassified as type 1 or type 2 diabetes. Insulin treatment is often not needed.[95]
INVESTIGATIONS
Genetic testing in people with high index of suspicion (genes encoding glucokinase and transcription factors are identified).[96]
Ketosis-prone diabetes
SIGNS / SYMPTOMS
Presents with unprovoked ketosis or ketoacidosis but with a subsequent course that more closely mirrors type 2 than type 1 diabetes.[68][97]
Considered an 'idiopathic diabetes', as patients have no evidence of autoimmunity. Often misclassified as type 1 diabetes, as individuals have episodic ketoacidosis and exhibit varying degrees of insulin deficiency between episodes. However, a type 2 diabetes phenotype is common in high-income countries (obesity, insulin resistance, metabolic syndrome) although a similar presentation has also been seen in lean individuals in low-income countries.[68][98]
Patients are usually from a minority ethnic group, and have a positive family history of diabetes.[98]
On discontinuation of insulin therapy, the period of near-normoglycaemic remission may last for a few months to several years. However, almost half will be insulin dependent 10 years after diagnosis.[97]
INVESTIGATIONS
Absent islet cell auto-antibodies.
C-peptide often low or undetectable during diabetic ketoacidosis; recovery may be used as reliable predictor of insulin discontinuation.[98]
Diabetes, gestational
SIGNS / SYMPTOMS
Only occurs during pregnancy.
INVESTIGATIONS
Gestational diabetes is generally detected by screening during pregnancy. The UK National Institute for Health and Care Excellence recommends offering testing for gestational diabetes to any pregnant woman with one or more of the following risk factors: BMI >30 kg/m²; previous macrosomic baby weighing ≥4.5 kg; previous gestational diabetes; first-degree relative with diabetes; ethnic background associated with high prevalence of diabetes.[99]
When overt hyperglycaemia occurs during pregnancy, it may be difficult to distinguish between undetected pre-existing type 2 diabetes and gestational diabetes.
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