Description
Diabetes mellitus (DM) is a group of metabolic diseases characterised by hyperglycaemia due to defects in insulin secretion, insulin action, or both. The chronic hyperglycaemia of diabetes leads to long-term damage, dysfunction, and failure of various organs. Diabetic embryopathy is a collection of birth defects that occur in foetuses of diabetic mothers due to uncontrolled maternal hyperglycaemia early in pregnancy.
Pathogenesis
The pathogenesis of DM involves a deficiency in insulin production (Type 1) or a resistance to the action of insulin (Type 2). Diabetic embryopathy is a result of maternal hyperglycaemia leading to a hyperglycaemic intrauterine environment, resulting in developmental abnormalities in the foetus. The exact mechanisms remain unclear, but it involves oxidative stress, increased apoptosis, and disruption of normal embryonic signalling pathways.
In the case of Type 1 DM, there is a strong genetic component involved. The disease is linked to certain human leukocyte antigen (HLA) genotypes, particularly the class II genes HLA-DQA1, HLA-DQB1 and HLA-DRB1. Of these, specific alleles such as HLA-DR3 and HLA-DR4 have been found to be most significantly associated with Type 1 DM. These genes encode proteins that present antigens to T-cells, triggering an immune response. Certain variants of these HLA genes are associated with an increased risk of developing Type 1 DM.
In individuals possessing these risk-associated HLA genotypes, the risk of developing Type 1 DM can be up to 5 times higher than in the general population. Conversely, some HLA genotypes, such as HLA-DR2, are associated with a reduced risk of Type 1 DM.
In addition to the HLA genes, several non-HLA genes have also been implicated in the pathogenesis of Type 1 DM, including the insulin gene (INS) and the protein tyrosine phosphatase, non-receptor type 22 gene (PTPN22).
Despite these genetic associations, the onset of Type 1 DM is believed to involve an environmental trigger in genetically susceptible individuals, leading to the autoimmune destruction of pancreatic beta cells.
Subtypes
- Type 1 DM: Characterised by the autoimmune destruction of the pancreatic beta cells
- Type 2 DM: Characterised by insulin resistance and relative insulin deficiency
- Gestational DM: Hyperglycaemia with onset or first recognition during pregnancy
Epidemiology, Risk Factors & Associations
- Type 1 Peak age of onset is between 10 and 14 years.
- Type 2 DM is the most common form (90-95%)
- Risk factors include obesity, physical inactivity, poor diet, family history, and age >45 years
- Associations include hypertension, dyslipidemia, and cardiovascular disease
- The HLA complex on chromosome 6 is the strongest genetic risk factor for Type 1 DM (40–50%). The DR-DQ haplotypes conferring the highest risk are DR3 and DR4
- Diabetic embryopathy is most commonly associated with poor glycemic control in early pregnancy
Clinical Features
- Polyuria, polydipsia, unexplained weight loss (Type 1 DM)
- Often asymptomatic in early stages, may present with complications such as retinopathy, nephropathy, neuropathy (Type 2 DM)
- Birth defects in infants of diabetic mothers can range from minor anomalies to severe, life-threatening malformations.
Complications
- Microvascular complications: nephropathy, neuropathy, and retinopathy
- Macrovascular complications: increased risk of cardiovascular, cerebrovascular, and peripheral vascular disease
- Diabetic embryopathy: congenital heart defects, neural tube defects, caudal regression syndrome (most characteristic)
Pathological Features
Histopathology
- Macroscopic: Pancreas may appear normal or show signs of chronic inflammation (fibrosis)
- Microscopic: Reduction or absence of insulin-secreting beta cells in the pancreatic islets (Type 1 DM); amyloid deposits in the islets (Type 2 DM)
Serology
- Increased HbA1c, increased fasting glucose
Biochemistry
- Elevated glucose levels in the urine
Radiological Features
General Features
- Characteristically demonstrate systemic effects of uncontrolled diabetes: vasculopathy, neuropathy, and organ damage (e.g., renal, ocular)
- Diabetic embryopathy: Congenital anomalies, most characteristic is caudal regression syndrome (sirenomelia)
CT
- Non-contrast: May demonstrate complications such as cerebrovascular disease, nephropathy, and peripheral artery disease
- Contrast-enhanced: Useful in evaluating cardiovascular disease and diabetic nephropathy
MRI
- T1WI: Useful in evaluating diabetic retinopathy and nephropathy
- T2WI: Useful in assessing diabetic neuropathy
- T1 C+: Can be used in assessing cardiovascular disease
- DWI/ADC: Not typically used in the evaluation of diabetes
US
- B-mode: May demonstrate atherosclerotic changes in peripheral vessels, renal changes in diabetic nephropathy
- Colour Doppler: May demonstrate decreased flow in peripheral vessels in severe peripheral arterial disease
NM
- PET FDG: Not typically used in the evaluation of diabetes
Grading and Staging
Grading is based on HbA1c levels (optimal, suboptimal, poor) and complications are staged based on organ involvement.
Diagnosis
Diagnosis is based on clinical symptoms and confirmed by blood glucose levels: fasting glucose, HbA1c, or an oral glucose tolerance test.
Differential Diagnosis
- Stress-induced hyperglycaemia
- Pancreatic disease
- Drug-induced hyperglycaemia
Management
Management includes lifestyle modifications, antihyperglycemic medications, insulin therapy, and regular monitoring for complications. Regular antenatal care and good glycemic control in early pregnancy can prevent diabetic embryopathy.