Lecture 8: Diabetes And Hypoglycemia Flashcards
What is diabetes mellitus?
- Includes a heterogenous group of disorders characterized by the presence of hyperglycemia (high blood glucose levels) due to defective secretion of insulin OR action of insulin OR both
- Diabetes affects many organs – can result in blindness, renal failure, cardiovascular disease, stroke ……
- There is a worldwide increase in the incidence of Diabetes mellitus (concomitant with the incidence of obesity) - ‘DIABESITY’
What is type 1 diabetes mellitus?
- Autoimmune destruction of pancreatic β-cells, progressive destruction and marked reduction in insulin secretion
- Insulin levels: Very low or absent; Very low C-peptide
- 10% of patients with diabetes mellitus
- Age of onset: Adolescence (young adults)
- Abrupt onset when loss of 80-90% of beta-cells
- Ketoacidosis common complication
- Life-long insulin therapy to prevent complications (Ketosis)
What are the risk factors for type 2 diabetes mellitus?
• Risk factors:
• Abdominal obesity (Syndrome X/ Metabolic syndrome/ insulin resistance
syndrome/ central obesity) • Sedentary lifestyle
• And aging
Whaat happens in type 2 diabetes?
- Target tissues (liver, skeletal muscle & adipose tissue) do not respond to circulating insulin (insulin resistance) and decrease in insulin secretion (decreased insulin secretion)
- Oral hypoglycemic agents and insulin may be required in later stages
- Ketoacidosis – not as common as in type 1
- Obesity in children - type 2 diabetes in children. Insulin resistance rather than insulin deficiency. Major public health concern
What is the significance of insulin resistance in diabetes?
- Less-than-expected (suboptimal) biological effect of insulin
- 200 U of insulin/day for glycemic control
- Anthropometric risk factors
- BMI > 30 (obesity)
- Higher waist circumference (Central obesity)
- Waist to hip ratio (WHR) greater than 1 (Abdominal obesity)
- In central obesity, (most common cause of insulin resistance)
- Decreased number of insulin receptors • And a post-receptor failure
How is adipocytes an endocrine organ?
• Storage organ for triacylglycerols
• Weight gain (central obesity) results in
Decreased Adiponectin
• Increased secretion of leptin
• Reduced secretion of adiponectin
• Secretion of pro-inflammatory cytokines
• Contribute to insulin resistance
Explain the impact of adipocytes as an endocrine
Increased leptin
- appetite & energy balance
- reproduction
- insulin sensitivity
- immunity
Decreased Adiponectin
-insulin sensitivity
Pro-inflammatory cytokines
-insulin sensitivity
Angiotensinogen
-blood pressure
PAI-1
-haemostasis
Describe the mechanism of insulin resistance
Insulin resistance in central obesity
– Reduced adiponectin levels: Impairs fat metabolism
– Elevated leptin (leptin resistance) impairs insulin action
– Elevated free fatty acids from visceral adipose tissue • Impairs action of insulin on liver
• Reduce glucose utilization and cause hyperglycemia
• Impairs insulin secretion from pancreas
– Low glucagon like peptide-1 (GLP-1):
Incretin stimulates insulin secretion. Incretins released
from intestinal endocrine cells
(refer pg 310; c. Gastrointestinal hormones)
– Pro-inflammatory cytokines (IL-6, TNF-alpha)
Describe the progression of type 2 diabetes mellitus
Initial stages, hypersecretion of insulin (insulin resistance), target tissues not responsive to insulin (fewer insulin receptors/ post-receptor defect). Later stages, decreased (suboptimal) insulin secretion from β-cells (β-cell
dysfunction) with insulin resistance
- Obese individuals develop insulin resistance, which may precede the development of diabetes by 10 or more years
- Patients diagnosed with type 2 diabetes initially show insulin resistance with compensatory hyperinsulinemia
- Subsequently, B-cell dysfunction occurs, marked by declining insulin secretion and worsening hyperglycemia
What are the presenting features of diabetes mellitus ?
- Classical triad: Polyphagia, Polydipsia, & Polyuria - more common in type 1
- Weight loss (type 1) – Accelerated lipolysis and muscle proteolysis
- Ketoacidosis more common in type 1
- Insulin deficiency leads to increased muscle proteolysis and negative nitrogen balance. (Remember, insulin facilitates entry of amino acids into muscle and increases protein synthesis)
- Insulin deficiency results in adipose tissue lipolysis (Remember, insulin favors storage of TAG)
- Decreased secretion of insulin due to beta-cell destruction→ Hyperglycemia
- Diabetes mellitus affects carbohydrate, lipid and protein metabolism
What are the presenting features of type 2 diabetes mellitus?
- Many type 2 diabetics are obese (insulin resistance)
- Insidious/ asymptomatic onset – detected by screening tests • Hyperglycemia present for many years before symptoms
- Typical symptoms: frequent changes in vision (prescription glasses); repeated infections; polyuria and polydipsia
Summarize mechanism of hyperglycemia in type 1 and type 2 diabetes mellitus
Decreased number of insulin receptors/ post receptor defects (insulin resistance)
Increased glucose production by liver
Decreased number of GLUT-4 in peripheral tissues
Decreased secretion of insulin from the pancreas
Explain the dyslipidemia in insulin resistance and type 2 diabetes mellitus
• Lipoprotein abnormalities commonly observed are
• Increased small dense LDL (LDL-B) - atherogenic
• Decreased HDL levels
• Increased serum triacylglycerol (Increased VLDL) – reduced activity of lipoprotein
lipase – Remember, lipoprotein lipase requires insulin for optimum activity
• Atherogenic lipid profile →atherosclerosis (macrovascular) - Cardiovascular disease
• Increased circulating free fatty acids due to increased breakdown of TAGs in adipose tissue – contributes to insulin resistance and reduced insulin secretion
• Markers indicating insulin resistance • Elevated serum free fatty acids
• Increased serum TAG: HDL ratio
What are the laboratory tests for diagnosis and long-term management of diabetes mellitus?
- Fasting plasma glucose > 126 mg/dL: Screening test – 8 hours after meal • Random plasma glucose (>200mg/dL) with one of symptoms
- Elevated HbA1c levels >6.5%
- Oral glucose tolerance test (OGTT)
- Evaluates the ability to regulate glucose metabolism
- Considered as the ‘gold standard test’
- Used to identify patients with ‘prediabetes’ and gestational diabetes • 2-hour plasma glucose >200mg/dL after 75 gms of glucose (OGTT)
What is the significance of HBA1c?
- Non-enzymatic glycation of hemoglobin (depends on plasma glucose levels)
- Indicator of long-term glucose control (Over previous 3-4 months)
- Poor blood glucose control (high HBA1c), higher risk of complications (microvascular and macrovascular)
- Optimal blood glucose control reduces risk of complications
- Used for diagnosis of diabetes mellitus – greater than 6.5%
Summarize medical nutrition therapy
- Medical nutrition therapy • Dietary modifications
- Weight reduction
- Exercise and lifestyle modifications
- Oral hypoglycemic agents
- Insulin injections (type 1 and in later stages of type 2 diabetes)