EN08 - Diabetes

What is diabetes mellitus (DM)?

A group of heterogeneous multifactorial metabolic disorders characterized by hyperglycemia due to impaired insulin production, defective insulin action, or both.

What percentage of people in Michigan have diabetes?

12% diabetics.

What percentage of people in Michigan are pre-diabetic?

35% pre-diabetics.

What are the laboratory tests for diabetes?

Plasma glucose concentration, oral glucose tolerance test (OGTT), and glycated hemoglobin (HbA1c).

What is fasting plasma glucose (FPG)?

Plasma glucose concentration measured after 8 hours of fasting.

What is the normal fasting plasma glucose level?

Less than 100 mg/dL (5.6 mmol/L).

What is the oral glucose tolerance test (OGTT)?

Measurement of glucose concentration 2 hours after oral ingestion of 75 g glucose.

What is glycated hemoglobin (HbA1c)?

A measure of average blood glucose over approximately 8–12 weeks.

What causes HbA1c formation?

Post-translational glycation of hemoglobin A (HbA).

What determines the degree of HbA1c glycation?

It is proportional to the amount of glucose.

Why does HbA1c remain in circulation for a long time?

Glycation is irreversible, so HbA1c persists for the entire life of the red blood cell.

What is HbA1c used for?

Monitoring glycemic control.

What is a normal HbA1c level?

Less than 6%.

What is the recommended HbA1c level for diabetics?

Approximately 7%.

What are the criteria for prediabetes based on fasting plasma glucose?

100–125 mg/dL.

What are the criteria for prediabetes based on OGTT?

2-hour plasma glucose 140–200 mg/dL.

What is the HbA1c range for prediabetes?

5.8–6.5%.

What are the main categories of diabetes mellitus?

Primary (idiopathic), gestational diabetes, and secondary diabetes.

What percentage of diabetes cases are Type 1 diabetes (T1DM)?

Approximately 10%.

What is the typical age of onset for T1DM?

Young onset (<35 years), mostly around 12 years old.

What is latent autoimmune diabetes in adults (LADA)?

Adult-onset autoimmune diabetes accounting for 1–5% of cases.

What percentage of diabetes cases are Type 2 diabetes (T2DM)?

Approximately 90%.

What is the typical age of onset for T2DM?

Adult onset (>35 years), often linked to obesity.

What is maturity-onset diabetes of the young (MODY)?

A young-onset form of T2DM (1–5%) often due to genetic defects such as glucokinase deficiency.

What is gestational diabetes (GDM)?

Diabetes that develops during pregnancy.

What is secondary diabetes?

Diabetes resulting from other underlying conditions or causes.

What is the main cause of Type 1 diabetes mellitus?

Autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency.

What genetic factors are associated with T1DM?

Gene variants at the HLA locus, especially HLA-DR3 and HLA-DR4.

What percentage of T1DM patients have HLA-DR3 or HLA-DR4 variants?

Approximately 90%.

What is the pattern of heritability in T1DM?

Stronger paternal heritability (6% risk if father affected vs 3% if mother affected).

What is the concordance rate for monozygotic twins in T1DM?

25–50%.

What environmental factors are associated with T1DM?

Viral infections such as rubella virus.

What are islet cell cytoplasmic autoantibodies (ICCA)?

Autoantibodies present in approximately 90% of T1DM patients.

What are islet cell surface autoantibodies (ICSA)?

Autoantibodies present in approximately 80% of T1DM patients.

What percentage of T1DM patients have antibodies against insulin?

Approximately 40%.

What happens to immunological markers over time in T1DM?

They decline with time.

What is the classic triad of symptoms in T1DM?

Polydipsia, polyuria, and polyphagia.

What additional symptoms are seen in T1DM?

Weight loss and fatigue.

What metabolic processes increase in T1DM due to insulin deficiency?

Protein degradation, gluconeogenesis, glycogenolysis, and lipolysis.

What is the effect of increased gluconeogenesis and glycogenolysis in T1DM?

Increased glucose release from the liver causing hyperglycemia.

What happens to glucose uptake in muscle and adipose tissue in T1DM?

It decreases.

What is the result of increased lipolysis in T1DM?

Increased acetyl-CoA leading to hepatic ketone body production.

What condition results from excessive ketone body production in T1DM?

Ketoacidosis.

What happens to lipoprotein lipase activity in T1DM?

It decreases in peripheral tissues.

What is the result of decreased lipoprotein lipase activity?

Increased chylomicrons and VLDL leading to hypertriglyceridemia.

What is diabetic ketoacidosis (DKA)?

The most severe and life-threatening complication of T1DM.

What are the diagnostic features of DKA?

Metabolic acidosis, hyperketonemia or ketonuria, hyperglycemia, hyperventilation, and acetone-smelling breath.

What is the primary treatment for T1DM?

Exogenous subcutaneous insulin.

What is standard insulin therapy in T1DM?

2–3 injections per day.

What glucose and HbA1c levels are seen with standard therapy?

Plasma glucose 250–275 mg/dL and HbA1c 8–9%.

What is intensive insulin therapy in T1DM?

More frequent monitoring and more than 4 injections per day.

What glucose and HbA1c levels are seen with intensive therapy?

Plasma glucose 150 mg/dL and HbA1c 7%.

What are the benefits of intensive insulin therapy?

50% reduction in vascular complications.

What is a risk of intensive insulin therapy?

Three-fold increase in hypoglycemic crises.

What is the emergency treatment for diabetic ketoacidosis?

Intravenous insulin, rehydration, and potassium (K⁺) supplementation.

What type of patients are typically affected by Type 2 diabetes mellitus (T2DM)?

Obese patients older than 40 years.

What is the heritability of T2DM?

High heritability (approximately 70%).

What symptoms are commonly seen in T2DM?

Mild symptoms such as polyuria and polydipsia.

How is T2DM often diagnosed?

During routine laboratory exams.

What causes hyperglycemia in T2DM?

Increased hepatic glucose production combined with decreased glucose uptake in adipose tissue and muscle.

Why does ketoacidosis usually not occur in T2DM?

There is sufficient insulin to prevent ketoacidosis.

What lipid abnormality is associated with T2DM?

Dyslipidemia.

What combination defines metabolic syndrome?

Obesity + T2DM + atherosclerosis (hypertension).

What is the treatment approach for T2DM?

Oral antidiabetics and lifestyle changes including diet and exercise (weight loss).

What are the two main pathogenic factors in T2DM?

Insulin resistance and dysfunctional beta cells.

What is insulin resistance (IR)?

Decreased ability of target tissues to respond to circulating insulin.

What happens initially in response to insulin resistance?

Compensatory increase in insulin production.

What happens over time to beta cells in T2DM?

Progressive loss of function leading to decreased insulin secretion.

Why do beta cells fail in T2DM?

Long-term toxic effects of high plasma glucose and an inflammatory environment impair their function.

What is the result of beta cell dysfunction in T2DM?

Inability to secrete enough insulin to overcome hyperglycemia.

What are the three sites of insulin resistance?

Pre-receptor, receptor, and post-receptor.

What occurs at the pre-receptor level in insulin resistance?

Auto-insulin antibodies interfere with insulin action.

What occurs at the receptor level in insulin resistance?

Decreased number of receptor tyrosine kinase (RTK) receptors, reduced insulin binding, or insulin receptor mutations.

What occurs at the post-receptor level in insulin resistance?

Defective signal transduction.

How is obesity related to insulin resistance at the receptor level?

It is associated with a lower number of receptors.

What is the main defect in obesity-related insulin resistance?

Defective intracellular signaling.

What is the underlying mechanism of insulin resistance related to adipose tissue?

Adipokine secretion causing low-grade chronic inflammation.

What happens to leptin levels in obesity?

Leptin levels are high.

What is the effect of high leptin levels?

It is pro-inflammatory and stimulates IL-6 and TNF-alpha.

What is leptin’s normal physiological role?

Acts as a satiety signal and promotes energy expenditure.

What condition occurs despite high leptin levels in obesity?

Leptin resistance.

What is adiponectin?

An anti-inflammatory adipokine secreted exclusively by adipocytes.

What stimulates adiponectin expression?

Insulin.

What inhibits adiponectin expression?

Glucocorticoids.

What is the effect of adiponectin on inflammatory cytokines?

It reduces IL-6 and TNF-alpha expression.

What happens to adiponectin levels in obesity and T2DM?

They are low.

What is the primary defect in T1DM?

Immune destruction of beta cells.

What is the primary defect in T2DM?

Increased insulin resistance.

Is insulin treatment required in T1DM?

Yes, always.

When is insulin used in T2DM?

Only when oral agents and diet fail.

Is T1DM associated with obesity?

No.

Is T2DM associated with obesity?

Usually yes.

What is the genetic predisposition in T1DM?

Weak, polygenic.

What is the genetic predisposition in T2DM?

Strong, polygenic.

What HLA associations are seen in T1DM?

HLA-DR3 and HLA-DR4.

Are HLA associations seen in T2DM?

No.

How severe is glucose intolerance in T1DM?

Severe.

How severe is glucose intolerance in T2DM?

Mild to moderate.

Is ketoacidosis common in T1DM?

Yes.

Is ketoacidosis common in T2DM?

Rare.