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Diabetes > Diabetes Mellitus – Treatment with diet, drugs and insulin > Flashcards

Diabetes Mellitus – Treatment with diet, drugs and insulin Flashcards

(43 cards)

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1
Q

Describe Type 1 Diabetes

A
  • Autoimmune destruction of islet beta cells
  • Insulin deficiency
  • Ketosis-prone
  • Seldom overweight
  • Diagnosed young, median age 9
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2
Q

Describe Type 2 Diabetes

A
  • Decreased beta cell mass and dysfunction of islets
  • Insulin resistance
  • Not ketosis-prone
  • Often overweight
  • Tends to be diagnosed in later life
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3
Q

What are the aims of diabetes treatment?

A
  • To restore disturbed metabolism to near normal
  • To prevent, or delay progression, of diabetic complications
  • To educate people about diabetes and motivate them to achieve effective self-management
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4
Q

What are the aims of dietary management in diabetes?

A
  • To achieve good glycaemic control
  • To reduce hyperglycaemia and avoid hypoglycaemia
  • To ensure adequate nutritional intake
  • To assist with weight management
  • To avoid aggravating diabetic complications
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5
Q

What are the calorific values of food constituents?

A
  • Carbohydrate= 4 kcals
  • Protein= 4 kcals
  • Fat= 9 kcals
  • Alcohol= 7 kcals
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6
Q

Describe a weight-reducing diet

A

-Reduce/ eliminate refined carbohydrates and saturated fat
-Restrict TOTAL caloric intake (portion size)
=Increase insulin sensitivity
=Lower blood glucose
=Lower triglycerides/ LDL-cholesterol

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7
Q

What is the Glycaemic Index?

A

-GLYCAEMIC INDEX (GI) is a measure of change in blood glucose following ingestion of a particular food
=Post-prandial rise in blood glucose is influenced by amount and source of carbohydrate

-Different carbohydrate-containing foods can be ranked by their effect on post-prandial glycaemia
=Low GI foods produce a slow, gradual rise in blood glucose after ingestion
=Low GI foods include starchy foods (rice, spaghetti, granary bread, porridge) and pulses like beans and lentils

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8
Q

What is the recommended composition of a healthy diet as % energy intake?

A
  • Carbohydrate= 45-60% (unrefined, complex)
  • Fat <35% (monosaturated 10-20%)
  • Protein= 10-15% (do not exceed 1g/kg body wt)
  • High intake of dietary fibre (fruit, vegetables), low intake of salt
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9
Q

Describe dietary treatment of Type 1 Diabetes

A
  • At diagnosis insulin should be started immediately
  • Dietary modification requires restriction of refined sugars and saturated fats
  • Diet is weight-maintaining for most people
  • Insulin dosage adjustment is based on carbohydrate content of meals
  • Structured education programmes are available, e.g. DAFNE (Dose Adjustment For Normal Eating)
  • Other lifestyle changes (regular exercise) are supplementary
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10
Q

What are the potential therapeutic targets in T2DM?

A
  • Adipose deposition
  • Liver (gluconeogenesis)
  • B-cell (dysfunction)
  • Kidneys= promote more release of glucose through urine
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11
Q

Describe the intensification of therapy in Type 2 Diabetes management

A
  • Diet and exercise
  • Oral monotherapy
  • Oral combination
  • Oral and insulin
  • Insulin
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12
Q

What are the indications and contraindications for oral hypoglycaemic drugs?

A

-Indications= T2DM (if diet alone inadequate)
=Insulin sensitizers in combination with insulin Type 1
-Contraindications= ketoacidosis, severe intercurrent illness

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13
Q

Describe sulphonyreas (T2DM)

A
  • stimulate secretion of endogenous insulin
  • used in non-obese patients (may be insulin-deficient)
  • used as monotherapy or in combination with metformin, glitazone or insulin
  • Glipizide (intermediate duration of action), gliclazide (older patients as shorter duration)
  • choice of sulfonylurea is based on duration of action and method of elimination
  • promote weight gain
  • main adverse effect is hypoglycaemia
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14
Q

Describe Biguanide/ Metformin (T2DM)

A
  • decreases hepatic glucose production
  • increases insulin sensitivity in muscle
  • encourages weight loss
  • effective as monotherapy or in combination with sulfonylurea, glitazone or insulin
  • side-effects include nausea and diarrhoea
  • contraindicated in renal impairment (risk of lactic acidosis)
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15
Q

Describe Glucose Prandial Regulators (Glinides)

A
  • Repaglinide (MEGLITINIDE)
  • Nateglinide (AMINO ACID DERIVATIVE)
  • Insulin secretagogues – direct effect on beta cells
  • Stimulate rapid endogenous insulin release when given with meals
  • Side-effects include weight gain and hypoglycaemia
  • Lower risk of hypoglycaemia than sulfonylureas
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16
Q

Describe a glucosidase inhibitors

A

-Acarbose, Miglitol
-Delay digestion of carbohydrate and slow down postprandial absorption of glucose
-Do not cause weight gain
Limited efficacy; can be used in combination
-Gastrointestinal side-effects are common, including bloating and flatulence

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17
Q

Describe how PPAR gamma works

A

-Work in fat (lipolysis reduced)
0-lower plasma free fatty acids, increases adiponectin
-increase insulin sensitivity/ reduces insulin resistance in liver and muscle
=reduces glucose output in liver
=Increases glucose uptake from muscle

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18
Q

Describe Thiazolidinedione

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A
  • Pioglitazone
  • Slow onset of action - take 2-3 months to achieve maximal effect (works at level of nucleus)
  • Promote weight gain - but redistribute body fat to reduce visceral depot
  • Contraindicated in congestive cardiac failure; hepatic impairment (water retention) May cause vertebral fractures
19
Q

What is the Incretin Effect?

Study These Flashcards
A

-Plasma insulin response to oral and IV insulin
=Secretion of insulin is greater in response to oral than IV
=Promoted by release of GI hormones “incretins”

20
Q

Describe Glucagon-like peptide (GLP-1)

Study These Flashcards
A
  • Potent insulinotropic hormone (incretin) is released in response to meals
  • Rapidly degraded in plasma by enzyme Dipeptidyl Peptidase 4 (DPP- 4)
  • Plasma GLP-1 is lower in people with impaired glucose tolerance (IGT) and type 2 diabetes compared to healthy non-diabetic subjects
21
Q

What are the physiological effects of GLP-1?

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A

-Upon ingestion of food, GLP-1 is secreted from the L-cells of the intestine
=Stimulates glucose-dependent insulin secretion
=Suppresses glucagon secretion
=Slows gastric emptying
=Reduces food intake
=Improves insulin sensitivity

22
Q

What are the therapeutic forms of GLP-1?

Study These Flashcards
A
  • Incretin mimetic, synthetic exendin-4 (Exenatide)
  • GLP-1 analogue (Liraglutide)
  • DPP- 4 inhibitors (Gliptins)
  • EXENATIDE: synthetic form of Exendin-4
23
Q

Describe incretin mimetics

Study These Flashcards
A
  • Exenatide, Liraglutide
  • Act like a GLP-1 peptide
  • Have to be given by injection
  • Promote weight loss
  • Given in combination with either metformin or sulfonylurea
  • Main side-effect is nausea
  • Hypoglycaemia rare except when given with SU
24
Q

Describe gliptins

Study These Flashcards
A
  • Sitagliptin, vildagliptin
  • DPP-4 inhibitors – inhibit degradation of incretin hormones and enhance their actions
  • Oral route of administration
  • Taken in combination with metformin
  • Produce modest reduction in HbA1c so less effective
  • Weight neutral
  • Few side-effects, with minimal hypoglycaemia
25
Describe SGLT2 inhibitors
-Sodium-glucose Cotransporter-2 inhibitors -acts as a glucuretic to remove glucose that would otherwise be reabsorbed =Lowers blood sugar =canagliflozin, dapagliflozin, and empagliflozin =Reduction in cardiovascular events?
26
What are the mechanisms and sites of actions for anti-diabetic drugs?
-Augment supply of insulin, pancreatic beta cell =Sulfonylureas =Prandial glucose regulators (glinides) =Incretin mimetics -Enhance insulin action and reduce resistance, liver fat and muscle =Metformin =Thiazolidinedione -Delay carbohydrate absorption, gut =a glucosidase inhibitors =Incretin mimetics
27
What are the indications for insulin therapy in T2DM?
- Persistently elevated blood glucose and HbA1c on maximum doses of anti-diabetic drugs (secondary failure to anti-diabetes drugs) - Symptoms of hyperglycaemia and/or infections (e.g. candidiasis) - Non-fasting ketonuria - Severe intercurrent illness - Metabolic complications (hyperosmolar states)
28
What are the problems with insulin therapy?
- Insulin has to be given by injection - Biological action is variable as insulin absorption is influenced by many factors (site of injection, ambient temperature, exercise, etc.) - Insulin has to be given several times daily - Insulin regimens are often complicated
29
What are the types and formulations of insulin?
- Short acting= soluble (actrapid, Humulin-S) - Intermediate-acting= isophane (NPH)= Insulatard, Humulin-I -Fixed mixtures are available containing combinations of soluble and isophane insulins e.g. 30% soluble with 70% isophane (Humulin M3)
30
What are insulin analogues?
- Substitution of single amino acid in insulin chain - Alters absorption characteristics of insulin - Time-action profile is modified by minor changes in amino acid sequence of insulin molecule
31
What are the types of insulin analogues?
- Fast-acting= insulin lispro (Humalog), aspart (Novorapid), glulisine (Apidra) - Long-acting= insulin glargine (Lantus), detemir (Levemir) -Fixed mixtures include Humalog Mix 25 (25% fast-acting) and Novomix 30 (30% fast-acting)
32
What are the time-action characteristics of insulins?
- Soluble= 30 mins onset, 1-2hrs peak effect, 7 hr duration - Fast-acting analogue= 5-10 mins onset, 30-60 mins peak effect, 3 hours duration - Isophane= 3hr onset, 7hr peak, 12-14hr duration - Long-acting analogue= 1hr onset, no peak effect, 19-32 hr duration
33
What does insulin regime choice depend on?
- Targets for glycaemic control - Time-action profile of insulins - Ease and convenience of administration - Flexibility of regimen - Practical issues (e.g. disability, supply, species preference)
34
What are the different insulin regimens for treating diabetes?
- BASAL-BOLUS (Multiple injection): Short-acting or fast-acting insulin before meals; intermediate-acting or long-acting insulin once daily - TWICE DAILY: Soluble or fast-acting and isophane (NPH) insulins combined; free-mixing or fixed mixture - ONCE DAILY: Intermediate-acting or long-acting insulin, combined with anti-diabetic drugs (Type 2 diabetes)
35
What are the routes of administration for insulin?
``` -SUBCUTANEOUS - =syringes, pens, pumps -intrapulmonary - =inhaler (historical) -intravenous, intramuscular =injection (emergency use) -intraperitoneal - =dialysate (renal failure) -transplanted islets =pancreatic islets ```
36
Describe lipohypertrophy at insulin injection sites
- Unsightly - Slows insulin absorption - Resolves if site avoided
37
What are the side effects of insulin therapy?
- HYPOGLYCAEMIA - WEIGHT GAIN - lipodystrophy at injection sites - peripheral oedema (salt & water retention) - insulin antibody formation (animal insulins) - local allergy (rare)
38
What are the signs and symptoms of hypoglycaemia?
-Blurred vision -Sweating -Hunger -Dizziness -Trembling -Palpitations =Low blood glucose (below 4 mmol/L)
39
What are the causes of insulin-induced hypoglycaemia?
-Administration of too much insulin -Inadequate consumption of food -Increased physical exercise -Alcohol (without food)= switches off gluconeogenesis =Mismatch occurs between plasma insulin and glucose concentrations
40
What are the risk factors for severe hypoglycaemia in Type 1 Diabetes?
-Duration of diabetes; Age (older); Gender (female) -Impaired awareness of hypoglycaemia =can't sense symptoms -History of previous severe hypoglycaemia -Strict glycaemic control =rate of hypoglycaemia increases -Sleep
41
What is the treatment for hypoglycaemia?
``` MILD (self-treated) -Oral fast-acting carbohydrate (10-15g) =glucose drink =glucose tablets, confectionery -Oral supplementary snack (starch) ``` ``` SEVERE (external help required) -Parenteral therapy =i.v. 20% dextrose (25-50g) =i.m. glucagon (1mg) -Oral therapy =buccal glucose gel; jam, honey ```
42
Describe morbidity associated with hypoglycaemia
``` -CNS =Coma, convulsions =Vascular events (stroke, transient ischaemia) =Cognitive impairment (young children) =Brain damage (rare) -Cardiac =Arrhythmias =Myocardial ischaemia/ infarct -Other =Accidents (including driving), injuries -Acquired syndromes =Impaired awareness of hypoglycaemia =Counterregulatory hormonal deficiencies ```
43
What are the reasons for difficulty achieving target HbA1c in T1DM?
- hypoglycaemia - inadequate fasting or post-prandial glycaemic control - wide glucose excursions - weight gain

Diabetes (30 decks)

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