Diabetes Mellitus Flashcards
Define diabetes
Group of metabolic diseases characterized by chronic hyperglycemia due to disorders of Carbohydrate, protein & fat metabolism & resulting from defects in Insulin secretion, Insulin action or both.
What are the acute complications is DM associated with?
Associated with acute complications
1. Hyperglycemic Hyperosmolar State (HHS),
2. Diabetic Ketoacidosis (DKA), Lactic Acidosis
3. Hypoglycemia
What are the long complications is DM associated with?
Retinopathy, Nephropathy, Neuropathy and Vasculopathy.
Epidemiology of diabetes
Globally, the number of people with DM has quadrupled in the past three decades and Diabetes mellitus is the 9th major cause of death. (WHO, 2019)
Diabetes presently causes 3.7-5 million deaths per year, mostly from cardiovascular diseases & it is expected to become the 7th leading cause of death globally by 2030.
About 1 in 10 adults worldwide now have diabetes mellitus, 95% of whom have T2DM ( 9.3% prevalence worldwide)
Although genetic predisposition partly determines individual susceptibility to DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic
537 million adults (20-79 years) are living with diabetes - 1 in 10. This number is predicted to rise to 643 million by 2030 and 783 million by 2045. Over 3 in 4 adults with diabetes live in low- and middle-income countries
Diabetes facts and figures show the growing global burden for individuals, families, and countries. The IDF Diabetes Atlas (2021) reports that 10.5% of the adult population (20-79 years) has diabetes, with almost half unaware that they are living with the condition.
What is the ADA & WHO, consensus classification?
TIDM- absolute Insulin deficiency, may be idiopathic or immune mediated,
T2DM-may range from predominantly insulin resistance with relative insulin deficiency to a predominantly insulin secretory defect with insulin resistance.
Other Specific Types of DM
GDM- DM during pregnancy, remits after delivery with return to frank T2DM in 50% of pts with GDM later in life.
What is the Etiologic Classification of DM?
- Type 1 DM:
- Immune mediated
- Idiopathic - Type 2 DM
- Other Specific Types
- Genetic defects of β-cell function
- Genetic defects in insulin action
- Diseases of the exocrine pancreas
- Endocrinopathies
- Drug or chemical induced
- Infections
- Uncommon forms of IMD (insulin-mediated diabetes)
- Other genetic syndromes sometimes associated with diabetes - GDM
Types of Genetic Defects DM
a) of beta cell function;
MODY 1-14
Types 1,3,5-hepatic transcription
Types 2,4 - mutation of Glucokinase and Islet cells
b) in Insulin action;
Type A insulin resistance, Leprechaunism, Rabson-Mendenhall syndrome, Lipodystophy Syndromes
Discuss disease of the Exocrine pancreas as a type of DM
Acute/Chronic Pancreatitis, Cystic fibrosis, Carcinoma, Hemochromatosis, Pancreatectomy, Fibrocalculous pancreatopathy.
How: CF causes thick mucus buildup in the pancreas, leading to fibrosis of pancreatic tissue and damage to insulin-producing beta cells in the islets of Langerhans.
Hemochromatosis causes diabetes, often referred to as “Bronze Diabetes,” due to excessive iron deposition in the pancreas, leading to insulin deficiency and insulin resistance.
Discuss diabetes caused by Endocrinopathies
increased insulin resistance; eg Cushings Syndrome, acromegaly, glucagonoma, Hyperthyroidism:
- decreased insulin secretion; eg somatostatinoma,
- affects both a/b; eg pheocromocytoma
OTHERS – Aldosteronoma
Discuss diabetes caused by drugs
a) increased insulin resistance-Glucocorticoids; Thyroid hormones
b) decreased insulin secretion-Thiazides, beta-adrenergic agonists
OTHERS DRUGS- Nicotinic acid, Protease Inhibitors, pentamidine, diazoxide, phenytoin, α-interferon, clozapine
CHEMICAL INDUCED DM
Vacor
Vacor is a rodenticide that can cause permanent diabetes mellitus by selectively destroying pancreatic beta cells, leading to insulin deficiency, similar to Type 1 Diabetes Mellitus (T1DM).
What are the Infections that cause DM (the 3 C’s) ?
- Congenital rubella
- Cytomegalovirus
- Coxsackie
Congenital rubella, cytomegalovirus (CMV), and coxsackievirus can all cause diabetes mellitus (virus-induced diabetes) by targeting pancreatic beta cells, leading to insulin deficiency. This is particularly linked to Type 1 Diabetes Mellitus (1DM), as these viruses can trigger autoimmune destruction of beta cells or directly damage them.
What are Uncommon forms of Immune-mediated DM?
a) “Stiff-person” Syndrome;
an autoimmune disorder of CNS;
Clinical feature: stiffness and painful muscle spasms,
High titres of GAD in Pancreas and CNS,
1/3 of patients develop β-cell dysfunction and DM
Why high titres of GAD?
- GAD (Glutamic Acid Decarboxylase) is an enzyme involved in GABA (gamma-aminobutyric acid) synthesis, a key inhibitory neurotransmitter in the CNS.
- It is found in both the brain and pancreas (in beta cells)
- In SPS autoantibodies attack GAD, which affects GABA production, causing muscle stiffness and spasms
- Because GAD is ALSO in the pancreas, the immune system also attacks beta cells causing insulin deficiency.
• High titers of GAD antibodies are found in both the pancreas and CNS, suggesting an autoimmune attack on these tissues.
b) Anti-insulin receptor Antibodies
What are Genetic syndromes associated with dm?
- Downs Syndrome
- Prader-Willi syndrome
- Klinefelter’s Syndrome
- Porphyria
- Turners Syndrome
- Friedreich’s ataxia
- Wolfram’s Syndrome
- DI+DM+Optic Atrophy+Deafness = DIDMOAD
How is diabetes diagnosed?
- Symptoms of diabetes plus random blood glucose concentration ≥ 11.1mmol/L or
- Fasting Plasma Glucose ≥ 7.0mmol/L or
- Hemoglobin A1c (HbA1c) ≥ 6.5% or
- 2-h plasma glucose ≥ 11.1mmol/L during an oral glucose tolerance test (OGTT)
Why HbA1c?
When blood sugar (glucose) is high, glucose attaches to hemoglobin, forming glycated hemoglobin (HbA1c).
• The higher the blood sugar levels, the more HbA1c is formed.
• Since red blood cells live for about 3 months, HbAlc shows average blood sugar levels over that time.
How can we determine pre-diabetes?
IFG (impaired fasting glucose) FPG 6.1 to 6.9 mmol/L
IGT (impaired glucose tolerance) - Random blood glucose & 2hr post prandial between 7.8 and 11.0mmol/L
What are the new values for diagnosis of Hyperglycemia?
Diabetes
fasting 7.0mmol/L & above
RBG & 2hr post prandial ≥ 11.1mmol/L
If above occurs on 2 seperate occasions and patient is asymptomatic = DM
What is Type 1 DM?
What are the symptoms?
Type 1 diabetes (previously known as insulin-dependent, juvenile or childhood-onset) is characterized by deficient insulin production and requires daily administration of insulin.
In 2017 there were 9 million people with type 1 diabetes; the majority of them live in high-income countries.Neither its cause nor the means to prevent it are known
Symptoms include:
* excessive excretion of urine (polyuria), thirst (polydipsia)
* constant hunger (polyphagia)
* weight loss
* vision changes
* and fatigue.
These symptoms may occur suddenly
How does T1DM present (characteristics)?
Characteristics;
- Young age, usually <30yrs & thin,
- rapid onset with severe symptoms
- Blood glucose high with ketonuria (due to the body using fat instead of glucose for energy resulting in production of ketones) ,
- mainly auto-immune etiology
presence of antibodies to Islet cells
association with HLA-haplotypes DR3/4, DQb-chain,
- concordance is ~50% in identical twins.
- Requires Insulin for survival.
- Rarely presents with poor wound healing / Long-term DM specific complications.
How do T2DM present?
T2DM
- Most common,~90% of DM,
- Strong genetic basis (polygenic); no association with HLA (because it’s not an autoimmune disease like T1DM)
- beta-cell dysfunction (?genetic), with reduced secretion and increased resistance
- Presents classical symptoms, of gradual onset,
- Age of onset ~30yrs, obese, +ve family hx
- Relative Insulin deficiency, Strong genetic basis is polygenic
- Diagnosed 5-7yrs after onset of impaired glycaemia.
- Uncommonly present with Ketosis as preserved insulin suppresses ketogenesis.
- Doesn’t require Insulin for survival.
- From the TRIUMVIRATE to the OMINOUS OCTET
What are the RISK FACTORS FOR TYPE 2 DM?
- Family History of Diabetes (1st degree relative)
- Obesity/Overweight (BMI>25mg/m2)
- Habitual Physical Inactivity
- Race/ethnicity (e.g. African American, Latino, * Native American, Asian American, Pacific Islander)
- Previously identified IFG or IGT
- History of GDM / Delivery of Macrosomic baby (≥4kg) / Peri uterine deaths
- Hypertension (BP ≥ 140/90mmHg)
- Dyslipidemia (HDL < 35 mg/dl (0.90mmol/L) and/or Tg level >250mg/dl)(2.82mmol/L)
- Polycystic Ovarian Syndrome (PCOS)
- Acanthosis Nigricans
- History of vascular disease
Key Contributors to T2DM (IDF)
Urbanization
An ageing population
Decreasing levels of physical activity
Increasing overweight and obesity prevalence
How does GDM present?
- Dm discovered during pregnancy, btwn 24-28wks of gestation.
- Hx of GDM in previous pregnancies.
- Affects 3-5% of pregnant women.
- 50% dev T2DM in ~10yrs later in life,
- 95%revert to normoglycaemia 6/52wks after delivery.
- Like inT2DM, Insulin Resistance state heightened by placental hormones.
What is the daily secretion of insulin? What is its function? How is it secreted and how does it become insulin?
Insulin- daily secretion is 30units.
major culprit in utilization of the metabolic fuels by the liver,adipose tissue and skeletal muscles.
Has anabolic (mainly) and catabolic effects.
Secreted as pre-proInsulin ->Proinsulin. Proinsulin -> Insulin +C-peptide, this conversion is energy free and occurs within 2-4 hrs.
