Diabetic Care: Types, Complications, and Diagnosis

Comprehensive flashcards covering the pathophysiology, clinical presentations, classifications, complications, epidemiological data, diagnostic cutoffs, and self-monitoring strategies for Diabetes Mellitus.

How is diabetes mellitus clinically defined?

A group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both.

How does the body restore glucose homeostasis when blood glucose rises above $120\,mg\%$ after a carbohydrate-rich meal?

Beta ($\beta$) cells of the pancreas are stimulated to release insulin into the blood, prompting body cells to take up more glucose and the liver to take up glucose and store it as glycogen.

How does the body restore glucose homeostasis when blood glucose falls below $80\,mg\%$ during fasting or after skipping a meal?

Alpha ($\alpha$) cells of the pancreas are stimulated to release glucagon into the blood, prompting the liver to break down glycogen and release glucose into the bloodstream.

What is Type 1 Diabetes Mellitus (T1DM)?

An autoimmune condition characterized by the destruction of insulin-producing $\beta$-cells in the pancreas, leading to absolute insulin deficiency.

What percentage of all diabetes cases does Type 1 Diabetes Mellitus account for, and what is its typical age of onset?

It affects approximately $5\%\text{ to }10\%$ of all diabetes cases and is typically diagnosed in children, adolescents, and young adults, though it can occur at any age.

Which specific Human Leukocyte Antigen (HLA) gene variants are associated with an increased susceptibility to Type 1 Diabetes?

$\text{HLA-DR3}$ and $\text{HLA-DR4}$.

What mutations in the insulin gene and insulin receptor can contribute to the development of Type 1 Diabetes?

Mutations in the coding sequence of the insulin gene that result in abnormal or non-functional insulin proteins, mutations that interfere with the cleavage of proinsulin, and mutations in the insulin receptor that impair insulin binding and reduce biological responsiveness.

Which environmental and viral factors have been implicated in triggering Type 1 Diabetes?

Viral infections including cytomegalovirus (CMV), Epstein-Barr virus (EBV), and enterovirus, as well as potential factors like lack of breastfeeding and environmental toxins.

What are the three classic osmotic symptoms of diabetes presentation, and what does each term mean?

Polydipsia (excessive thirst), polyuria (excessive urination, especially nocturia), and polyphagia (increased appetite/hunger).

What general symptoms, besides the classic triad of polyuria, polydipsia, and polyphagia, frequently characterize the clinical presentation of diabetes?

Unusual weight loss, extreme tiredness, nausea or vomiting, blurred vision, frequent bladder, vaginal, and skin infections, numbness or pain in the hands/legs, and slow healing of wounds.

What is Diabetic Ketoacidosis (DKA), and what primary metabolic defect causes it?

A potentially life-threatening acute complication of diabetes caused by severe insulin deficiency, where lack of insulin to suppress lipolysis causes the breakdown of triglycerides and free fatty acids into acidic ketone bodies.

In Diabetic Ketoacidosis (DKA), which catabolic counter-regulatory hormones are hypersecreted when cells are starved of glucose?

Glucagon, epinephrine, cortisol, and growth hormone (GH).

At what blood glucose threshold does renal filtration exceed tubular reabsorption, causing glucosuria and subsequent osmotic diuresis in DKA?

At a blood glucose concentration greater than $12\,mmol/L$.

What causes Kussmaul respiration in Diabetic Ketoacidosis, and what is its clinical presentation?

It is deep, fast breathing caused by the respiratory center blowing off $CO_2$ in an effort to compensate for and offset metabolic acidosis.

What is the physiological cause of the 'fruity breath' observed in patients presenting with Diabetic Ketoacidosis?

The exhalation (breathing off) of volatile ketone bodies formed during ketogenesis.

What is the typical magnitude of fluid deficit experienced by a patient with severe dehydration during Diabetic Ketoacidosis?

Up to $4\text{ to }5\,L$ dry.

What are the five main steps outlined for the clinical treatment of Diabetic Ketoacidosis (DKA)?

1. Administer aggressive IV fluids (+++ fluids).
2. Administer IV insulin plus $KCl$.
3. Follow the anion gap until it closes.
4. Identify and manage the precipitating cause.
5. Treat hypophosphatemia ($\text{low } PO_4$), which typically occurs hours to a day after ketosis resolves due to increased ATP production.

What is the critical rule for potassium ($KCl$) replacement during insulin therapy in Diabetic Ketoacidosis?

To prevent hypokalemia (as insulin shifts $K^+$ intracellularly), administer IV $KCl$ alongside IV insulin as soon as serum $[K^+] < 5.0\,mmol/L$, provided the patient has adequate renal function and urine output.

What is the clinical definition of Type 2 Diabetes Mellitus (T2DM)?

A chronic metabolic disorder characterized by insulin resistance and progressive pancreatic $\beta$-cell dysfunction, resulting in hyperglycemia.

What proportion of all diabetes cases does Type 2 Diabetes Mellitus represent?

Approximately $90\%\text{ to }95\%$ of all diabetes cases.

What cellular mechanisms lead to insulin resistance in Type 2 Diabetes Mellitus?

A reduction in the number of insulin receptors on target tissues and post-receptor signaling defects in pathways normally stimulated by insulin (such as glucose transport and glycogen synthesis), preventing efficient cellular glucose uptake.

How does pancreatic beta-cell function change over time in the progression of Type 2 Diabetes Mellitus?

The pancreas initially overproduces insulin as a compensatory response, but over time the $\beta$-cells become overworked, impaired, and fail to meet the increased insulin demand, leading to persistent hyperglycemia.

What are the primary modifiable risk factors for Type 2 Diabetes Mellitus?

Obesity (particularly central/abdominal obesity), a sedentary lifestyle (lack of physical activity), an unhealthy diet (high intake of processed carbohydrates, sugar-sweetened beverages, and unhealthy fats), and smoking.

What are the non-modifiable risk factors for Type 2 Diabetes Mellitus?

Advancing age (especially greater than $40$ years), family history of diabetes, and high-risk ethnicities (specifically individuals of Indian and Malay descent in Singapore).

According to epidemiological data from Singapore, how many individuals had diabetes in 2014, and what is the projected number for 2050?

$440,000$ Singaporeans had diabetes in 2014, and the number is projected to rise to $1,000,000$ by 2050.

What fraction of individuals living with diabetes in Singapore are unaware that they have the condition?

$1\text{ in }3$ individuals.

According to Singapore national registries, what proportions of stroke, heart attack, and new kidney failure cases are diabetes-related?

$2\text{ in }5$ stroke victims, $1\text{ in }2$ heart attack victims, and $2\text{ in }3$ new kidney failure cases are diabetes-related.

What is the projected economic burden of diabetes in Singapore among working-age adults from 2010 to 2050?

Healthcare costs and productivity losses are projected to rise from approximately $\$1.02\text{ million}$ in 2010 to $\$2.5\text{ billion}$ by 2050.

How is Gestational Diabetes Mellitus (GDM) defined?

A type of diabetes diagnosed during pregnancy, typically after $24$ weeks of gestation, in women who previously did not have diabetes.

What is the global prevalence of Gestational Diabetes Mellitus, and is the newborn born with diabetes?

It affects about $1\text{ in }10$ pregnancies globally, and the baby will NOT be born with diabetes.

What physiological changes during pregnancy drive increased insulin resistance and demand in GDM?

Placental secretion of anti-insulin hormones increases maternal insulin resistance, maternal hepatic glucose production increases by $15\%\text{ to }30\%$ late in pregnancy, and maternal insulin requirements rise up to three times normal levels.

What maternal risk factors increase the likelihood of developing Gestational Diabetes Mellitus?

Age older than $35$ years, obesity, sedentary lifestyle, unhealthy diet, smoking, family history, a previous child with macrosomia (birth weight $> 4\,kg$), personal history of prior GDM, and Chinese ethnicity.

What long-term metabolic risk do mothers diagnosed with Gestational Diabetes face following delivery?

A $50\%$ risk of developing Type 2 Diabetes Mellitus within $5\text{ to }10$ years after delivery.

What acute delivery complication is illustrated below, where fetal shoulder impaction occurs behind the maternal symphysis pubis?

Shoulder dystocia, a condition where the fetal head is delivered but one of the shoulders becomes lodged behind the mother's pubic bone.

What are the common fetal and neonatal complications associated with maternal Gestational Diabetes?

Macrosomia, stillbirth, miscarriage, birth defects, polyhydramnios, premature birth, neonatal hypoglycemia, respiratory distress syndrome, jaundice, and increased risk of future childhood obesity and glucose intolerance.

What are the primary lifestyle and pharmacological treatments for Gestational Diabetes Mellitus?

Lifestyle interventions (low-glycemic-index diet, limiting gestational weight gain, and exercise such as walking, cycling, and swimming); if hyperglycemia persists after $\ge 1\text{ to }2$ weeks, pharmacological therapy with insulin (the gold standard), metformin, or glibenclamide is initiated.

How are the long-term chronic vascular complications of diabetes classified?

Microvascular complications (diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy) and macrovascular complications (cardiovascular disease, cerebrovascular disease, and peripheral arterial disease).

How does chronic hyperglycemia induce microvascular damage at the level of endothelial cells and the basement membrane?

Hyperglycemia causes endothelial cell dysfunction and thickening of the capillary basement membrane, which impairs the diffusion of oxygen, nutrients, and waste products, leading to tissue ischemia, inflammation, and loss of anti-clotting factors.

What are Advanced Glycosylation End-products (AGEs), and what role do they play in diabetic complications?

Molecules formed when excessive glucose binds non-enzymatically to proteins and lipids; their accumulation causes intracellular dysfunction, oxidative stress, and chronic vascular inflammation.

How does chronic hyperglycemia compromise the mechanical properties of red blood cells (RBCs)?

Glucose binds to hemoglobin forming $HbA1c$, and along with oxidative stress, alters the RBC membrane flexibility, making it difficult for erythrocytes to deform and squeeze through narrow capillaries.

What structural retinal lesions define Stage 1 (Mild non-proliferative) and Stage 2 (Moderate non-proliferative) Diabetic Retinopathy?

Stage 1 features small vascular swellings called microaneurysms; Stage 2 features swelling that impedes blood flow, bleeding into the retina (hemorrhages), and deposits.

What pathological changes distinguish Stage 3 (Severe non-proliferative) from Stage 4 (Proliferative) Diabetic Retinopathy?

Stage 3 is marked by an increased number of microaneurysms, extensive hemorrhages, and vascular blockages depriving retina areas of blood; Stage 4 is characterized by neovascularization (growth of abnormal, fragile new vessels), scar tissue formation, retinal detachment, and potential blindness.

What is Diabetic Nephropathy, and what is its earliest detectable clinical indicator?

Kidney damage caused by hyperglycemia-induced injury to nephrons and glomeruli; its earliest indicator is microalbuminuria (small amounts of albumin leaking into urine).

What is the clinical progression of Diabetic Nephropathy if glycemic control remains poor?

Progression from microalbuminuria to macroalbuminuria, leading to progressive deterioration of filtration function, chronic kidney disease (CKD), and end-stage renal disease (ESRD) requiring dialysis or kidney transplantation.

What are the common symptoms of diabetic peripheral neuropathy, and what dangerous consequence do they lead to?

Pain, burning, tingling, numbness, and weakness primarily affecting the extremities (feet, legs, hands), which predispose patients to unnoticed injuries, non-healing diabetic foot ulcers, and lower limb amputations.

What clinical manifestations are caused by diabetic autonomic neuropathy?

Gastroparesis (delayed gastric emptying causing early satiety, bloating, and vomiting), constipation, neurogenic bladder (loss of bladder control), digestive issues, and resting tachycardia.

What is diabetic proximal neuropathy?

Nerve damage affecting the nerves in the hips, thighs, and legs, causing pain, weakness, and difficulty walking.

How does diabetes accelerate cardiovascular disease and coronary artery disease?

Endothelial injury combined with elevated levels of triglycerides and low-density lipoprotein (LDL) cholesterol promotes atherosclerosis; atherosclerotic plaques progressively narrow coronary arteries, reducing cardiac blood supply and increasing the risk of myocardial infarction.

What is the difference between a Transient Ischemic Attack (TIA) and a full ischemic stroke in cerebrovascular disease?

A TIA is a brief, temporary episode of neurological dysfunction caused by a temporary interruption of blood supply to the brain without permanent damage, whereas a stroke involves prolonged arterial blockage leading to permanent cerebral infarction and tissue death.

What is Peripheral Arterial Disease (PAD), and what percentage of patients with Critical Limb Ischaemia (CLI) have diabetes?

PAD is narrowing of peripheral arteries due to atherosclerosis, typically causing leg cramping and pain during activity that resolves with rest (intermittent claudication); approximately $50\%$ of patients with advanced CLI have diabetes and experience higher amputation and mortality rates.

What are the three main clinical purposes of screening and diagnostic testing in diabetes?

1. To diagnose diabetes (confirmed if glucose levels exceed threshold on two separate occasions).
2. To monitor glycemic control in previously diagnosed patients.
3. To screen asymptomatic individuals at high risk (e.g., overweight or positive family history).

How is a Fasting Plasma Glucose (FPG) test performed, and what does it measure?

Blood is sampled following an overnight fast of approximately $8\,hours$; it evaluates baseline insulin secretion and hepatic glucose production in the postabsorptive state without the influence of ingested food.

What are the diagnostic Fasting Plasma Glucose (FPG) thresholds for normal status, prediabetes, and diabetes mellitus?

Normal: Below $100\,mg/dL$ ($< 5.6\,mmol/L$). Prediabetes (Impaired Fasting Glucose): $100\text{ to }125\,mg/dL$ ($5.6\text{ to }6.9\,mmol/L$). Diabetes: $126\,mg/dL\text{ or higher}$ ($\ge 7.0\,mmol/L$).

What is the standard procedure for a diagnostic Oral Glucose Tolerance Test (OGTT) in non-pregnant individuals?

Conducted in the morning following an $8\text{ to }12\text{-hour}$ fast (no food, alcohol, or smoking); fasting blood is drawn at time point $0$, the patient drinks a solution containing $75\,g$ of anhydrous glucose within $5\,minutes$, and blood is drawn again at $120\,minutes$.

What are the 2-hour post-load glucose diagnostic thresholds for an OGTT in non-pregnant adults?

Normal: Below $140\,mg/dL$ ($< 7.8\,mmol/L$). Prediabetes (Impaired Glucose Tolerance): $140\text{ to }199\,mg/dL$ ($7.8\text{ to }11.0\,mmol/L$). Diabetes: $200\,mg/dL\text{ or higher}$ ($\ge 11.1\,mmol/L$).

What are the diagnostic cutoffs for Gestational Diabetes during a 75-gram, 2-hour OGTT, where exceeding any single value confirms the diagnosis?

Fasting: $\ge 92\,mg/dL$ ($\ge 5.1\,mmol/L$) 1-hour: $\ge 180\,mg/dL$ ($\ge 10.0\,mmol/L$) 2-hour: $\ge 153\,mg/dL$ ($\ge 8.5\,mmol/L$)

When is hyperglycemia in pregnancy classified as newly developed overt diabetes rather than Gestational Diabetes?

When the fasting plasma glucose is $\ge 126\,mg/dL$ ($\ge 7.0\,mmol/L$) or the 2-hour blood glucose is $\ge 200\,mg/dL$ ($\ge 11.1\,mmol/L$).

What are the diagnostic thresholds, indications, and limitations of a Random Blood Glucose test?

A value of $\ge 200\,mg/dL$ ($\ge 11.1\,mmol/L$) in a patient with symptoms indicates diabetes; it can be performed at any time of day for emergency assessment, but must be confirmed by FPG or OGTT and cannot be used to rule out/exclude diabetes.

What does the HbA1c test measure, why does it represent 2 to 3 months of glycemic history, and what are its diagnostic cutoffs?

It measures glycated hemoglobin ($Hb$ bound to glucose in RBCs), reflecting average blood glucose over the past $2\text{ to }3\,months$ ($6\text{ to }8\,weeks$) due to the $120\text{-day}$ lifespan of erythrocytes. Normal: Below $5.7\%$ ($< 39\,mmol/mol$). Prediabetes: $5.7\%\text{ to }6.4\%$ ($39\text{ to }47\,mmol/mol$). Diabetes: $\ge 6.5\%$ ($\ge 48\,mmol/mol$).

What clinical risk levels are indicated by blood ketone meter readings of < 0.6, 0.6-1.5, 1.6-2.9, and >= 3.0 mmol/L?

Below $0.6\,mmol/L$: Normal reading (green; no action required). $0.6\text{ to }1.5\,mmol/L$: Slightly increased risk of DKA (yellow; retest in a few hours). $1.6\text{ to }2.9\,mmol/L$: Increased risk of DKA (orange; contact GP or diabetes team promptly). $3.0\,mmol/L\text{ or higher}$: Very high risk of DKA (red; seek emergency medical care immediately).