Endocrinology Flashcards
Definition T1DM
Metabolic disorder characterised by hyperglycaemia due to absolute insulin deficiency. The condition develops due to destruction of pancreatic beta cells, mostly by immune-mediated mechanisms
Epidemiology T1DM
Accounts for about 5% to 10% of all patients with diabetes. It is the most commonly diagnosed diabetes of youth (under 20 years of age) and causes ≥85% of all diabetes cases in this age group worldwide.
More common in Europeans and less common in asians.
Highest incidence occurs in children 10-14 years with a slight male predominance particularly after puberty.
Aetiology T1DM
HLA-DR or HLA-DQ mutation can increase susceptibility.
Environmental factors
Human enterovirus
Risk Factors T1DM
Main:
Genetic predisposition
Others:
Infectious agents
Dietary factors
Medications
Pathophysiology T1DM
Autoimmune pancreatic beta-cell destruction in genetically susceptible individuals.
Beta-cell destruction proceeds sub-clinically for months to years as insulitis (inflammation of the beta cell). When 80% to 90% of beta cells have been destroyed, hyperglycaemia develops. Insulin resistance has no role in the pathophysiology of type 1 diabetes. However, with increasing prevalence of obesity, some patients with type 1 diabetes may be insulin resistant in addition to being insulin deficient.
Patients with insulin deficiency are unable to utilise glucose in peripheral muscle and adipose tissues. This stimulates the secretion of counter-regulatory hormones such as glucagon, adrenaline (epinephrine), cortisol, and growth hormone. These counter-regulatory hormones, especially glucagon, promote gluconeogenesis, glycogenolysis, and ketogenesis in the liver. As a result, patients present with hyperglycaemia and anion gap metabolic acidosis.
Long-term hyperglycaemia leads to vascular complications due to a combination of factors that include glycosylation of proteins in tissue and serum, production of sorbitol, and free radical damage. Microvascular complications include retinopathy, neuropathy, and nephropathy. Macrovascular complications include cardiovascular, cerebrovascular, and peripheral vascular disease. Hyperglycaemia is known to induce oxidative stress and inflammation. Oxidative stress can cause endothelial dysfunction by neutralising nitric oxide. Dysfunctional endothelium allows entry of low-density lipoprotein into the vessel wall, which induces a slow inflammatory process and leads to atheroma formation.
Clinical manifestations T1DM
Key Presentations
Hyperglycaemia, Polyuria, Polydipsia
Signs
Tachypnoea
Symptoms
Weight loss, blurred vision, nausea, dehydration, abdo pain, lethargic
Investigations T1DM
1st Line
Random plasma glucose - >= 11.1 mmol/L
Fasting plasma glucose - >= 7.0mmol/L
2 hour plasma glucose - >=11.1 mmol/L
Gold Standard
HbA1c - >= 6.5%
Others
Plasma or urine ketones - medium or high quantity
C-peptide (in unusual suspicion) - low
Autoimmune markers - autoantibodies to glutamic acid decarboxylase, insulin, islet cells, islet antigens (IA2 and IA2-beta), and the zinc transporter ZnT8 POSITIVE
Management T1DM
Daily basal bolus insulin - insulin detemir, glargine or degludec. Between 0.2-1.5 units/kg/day.
Pre-meal insulin correction dose - 1 unit lowers bg by 4mmol/L. Dependent on the units of daily bolus, levels prior to eating and amount of carbohydrates in the meal.
Metformin in 25 BMI or above 500mg daily for 1 week and up to 3 times daily.
Aspirin 75-150mg daily for pregnant T!DM women from 12 weeks up until birth of baby.
Consider Libre sensor or insulin pump for those who are young, unable to monitor themselves, work in a dirty environment etc.
Annual monitoring and reviews T1DM
HbA1c every 3 months <18 and 3-6 months in adults
Annual thyroid checkup
Eye examination for retinopathy every 1-2 years
BP annually
Foot health checkup for those at low risk annually
Regular dental examinations
Mental health assessments, especially for those at risk over body weight and shape.
Cardiovascular risk check annually - eGFR, urine ACR, smoking, BP, BG, full lipid profile, family history and abdominal adiposity.
Kidney screening annually fro those who have had T1DM for 5+ years.
Also discuss educational courses and check BG diary
Patient discussions include - exercise and alcohol consumption risk of hypoglycaemia even up to 24 hours after. E.g. do not exercise if ketones present and consider eating a snack without insulin prior. Monitory blood every 30 mins to an hour during activity.
Complications T1DM
DKA
Hypoglycaemia
Retinopathy
Diabetic kidney disease - glomerular mesangial sclerosis leading to proteinuria and progressive decline in glomerular filtration. Increased urinary albumin excretion (>30 mg/day) is the earliest sign of disease and a marker of much increased cardiovascular risk. Test yearly in people who have had type 1 diabetes for 5 years or more
Peripheral or autonomic neuropathy - distal symmetric polyneuropathy affecting sensory axons
Cardiovascular disease - high doses of insulin were associated with a less favourable cardiometabolic risk profile (higher body mass index, pulse rate, triglycerides, lower high-density lipoprotein [HDL] cholesterol) with hypertension secondary to underlying nephropathy.
Depression and other mental health issues including eating disorders
Prognosis T1DM
Untreated is fatal due to DKA
Chronic hyperglycaemia leads to many other co-morbidities which each have their own mortality rate.
leading cause of death before the age of 30 years was acute complications of diabete
Most women with T1DM have successful pregnancies.
DDx T1DM
T2DM
MODY - non-ketotic, non-insulin dependent diabetes that responds to oral glucose lowering drugs
Latent autoimmune diabetes in Adults LADA - Low to normal initial C-peptide level. Over 30YO
Definition T2DM
Progressive disorder defined by deficits in insulin secretion and increased insulin resistance that lead to abnormal glucose metabolism and related metabolic derangements.
Epidemiology T2DM
90% diabetes is type 2 with a global prevalence of 8.3%
Patients with type 2 diabetes have a very high risk of concurrent hypertension (80% to 90%), lipid disorders (70% to 80%), and overweight or obesity (60% to 70%).
More common later in life.
Aetiology T2DM
Genetic predisposition
High BMI
