Insulin and Diabetes Flashcards

Question

Gastric bypass

Answer 1

The goal of is to achieve and maintain a healthier body weight. Mean weight loss 2 years after gastric bypass is > 65% of excess weight loss (EWL) Most of the weight loss occurs in the first 6 months after surgery With a continuation of gradual loss throughout the first 18–24 months.

Answer 2

DAFNE (Type 1 Diabetes) DESMOND (Type 2 Diabetes)

Answer 3

Lose weight if overweight or obese Low Glycaemic Index carbohydrates An individualised approach to diet taking into consideration the person’s personal and cultural preferences Eat more of certain foods such as vegetables, fruits, wholegrains, fish, nuts and pulses Eat less red and processed meat, refined carbohydrates and sugar sweetened beverages.

Answer 4

The glycaemic index (GI) is a system of ranking carbohydrate-containing foods according to how quickly they affect blood glucose levels after a meal. Evidence: In patients with type 2 Diabetes following a low GI or low GI load diet results in a 0.5% reduction in HbA1c.

Answer 5

Fixed meal patterns Regular snacks Consistent amount of carbohydrate at meals Lighter lunch? Less flexibility and control for the patient

Answer 6

Non fixed meal patterns Regular snacks not required Variable amounts of carbohydrate at meals More flexibility and control for the patient More injections

Answer 7

Dose Adjustment For Normal Eating Nationally accredited structured education programme in intensive insulin therapy & self management. People with Type 1 diabetes are taught to match their insulin dose to their chosen food intake Basal bolus regime (1-2 injections of background insulin each day and quick acting insulin with meals Test blood glucose minimum of 4 times per day including before meals and before bed Type 1 Diabetes: Managed through insulin. For best control, adjust insulin to take account of: -Food (Carbohydrates) -Physical activity -Alcohol -Sickness. DAFNE: Group education course to teach patients insulin management.

Answer 8

Aims - Less guesswork. More freedom. Better health. - ↑ autonomy, competency & confidence. - Skills-based training for self management. Style - Person-centered. - Collaborative & interactive. Follows adult learning best practice: - “Experiential learning” (learning through reflection on doing) - Peer assisted learning. - Practical skill-based training.

Answer 9

Reduced HbA1c without increasing the risk of severe hypoglycaemia Benefits on both blood sugar control and psychological wellbeing after DAFNE remain at 1,2 and 7 years post course Severe hypoglycaemia is reduced by more than 60% producing cost savings through reduced paramedic call outs, A&E attendances and admissions

Answer 10

Previously treatment for type 1 diabetes involved two injections of insulin daily of containing a mixture of two types of insulin. The dose of insulin was fixed, therefore patients had to eat at the same time everyday and eat similar amounts of carbohydrates everyday. They also had to has a snack between meals to prevent hypos. Less flexible,

Answer 11

You would have two injections of background insulin injections daily - before bed and when getting up in the morning to provide this small continuous supply of insulin similar to the person without diabetes. By matching quick insulin to the food you eat Therefore they can eat different amounts of carbohydrates. E.g. breakfast during the week might have 2 slices of toast, In the weekend might have brunch with crossiant, fruit, cereal, yoghurt and toast. They can eat a different times of the day. 7am or weekends 10am. Having a snack becomes a choice, good if trying to lose weight. missing breakfast possible due to background insulin working to provide insulin

Answer 12

Sodium-glucose cotransporters (SGLTs) Secondary active transport SGLT1: glucose absorption from gut SGLT1, SGLT2: glucose reabsorption from kidney (PCT)

Answer 13

Family of glucose transporters (GLUTs) 1. GLUT 1 (brain, erythrocytes) – high affinity for glucose: constant uptake of glucose at 2-6 mM 2. GLUT 2 (liver, kidney, pancreas, gut) – low affinity: glucose equilibrates across membrane → Glucose-dependent insulin release in pancreas 3. GLUT 3 (brain) – high affinity 4. GLUT 4 (muscle and adipose tissue) – medium affinity. Insulin recruits transporters → Insulin-dependent uptake of glucose into cells

Answer 14

Clusters of endocrine cells surrounded by exocrine pancreas

Answer 15

α-cells (A cells): glucagon β-cells (B cells): insulin δ-cells: somatostatin

Answer 16

Original transcript: pre-pro insulin Signal sequence removed: proinsulin (in rough endoplasmic reticulum) Transfer to Golgi apparatus Peptidases break off the C peptide leaving an A and B chain linked by disulphide bonds One mole of C-peptide is secreted for each mole of insulin Significance of c-peptide is that it’s inert, and thus a good index of insulin secretion.

Answer 17

Pancreas supplied by branches of the coeliac, superior mesenteric, and splenic arteries. The venous drainage of the pancreas is into the portal system. Half of the secreted insulin is metabolized by the liver in it’s first pass; the remainder is diluted in the peripheral circulation C-peptide is more accurate index of insulin secretion in peripheral circulation (not metabolized by liver) Hepatic portal vein is only a fraction of the cardiac output, so insulin levels in the peripheral circulation (where you can easily sample) are much diluted. One mole of C-peptide is secreted for each mole of insulin

Answer 18

``` Incretin hormones -> ↑plasma glucose ↑ amino acids ↑ glucagon ↑ parasympathetic ↓ alpha adrenergic ↓ somatostatin ``` B cells release insulin

Answer 19

``` ↑ amino acids ↑ beta adrenergic ↑ parasympathetic ↓ plasma glucose ↓ insulin ↓ somatostatin ``` A cells release glucagon

Answer 20

No glucose receptor GLUT2 / Glucokinase can be thought of as the sensor Effector is rise in ATP due to glucose oxidation MAIN PATH- glucose entry to ATP production via glycolysis and TCA = closure of special K channel, which is ATP-gated (negatively) and consequent membrane depolarization. → increased Ca entry, and intracellular Ca → triggers insulin exocytosis. THUS anything that can depolarize the B cell, or otherwise raise intracellular Ca → insulin release. For example metformins, a common class of insulin-potentiating drugs, act to directly close the K/ATP channel, thus increasing insulin release by-passing the normal mechanisms. Also, parasympathetic stimulation can increase insulin release. This it due to muscarinic R activation, which via intracellular signalling, leads to Ca release from intracellular stores. Sympathetic stimulation, via alpha receptors, leads to a reduced sensitivity of the channel, leading to reduced likelihood of closure, and hence decreased inuslin release.

Answer 21

The insulin receptor is a member of the tyrosine kinase superfamily Insulin binding to its receptor Activates cascade of protein phosphorylation, which stimulate or inhibit specific metabolic enzymes by modulating enzyme phosphorylation Modulates activity of metabolic enzymes by regulating gene transcription Insulin binds to its receptor (1), → starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5), and fatty acid synthesis (6) (http://en.wikipedia.org/wiki/Insulin_receptor).

Answer 22

The insulin receptor is a disulfide-linked tetramer with the β-subunits spanning the membrane and the α-subunits located on the exterior surface. acetyl-CoA carboxylase (ACC). This is the enzyme that starts off lipogenesis, by converting acetyl CoA to malonly CoA. Note here that it’s under inhibitory control by PKA, which in turn depends on cAMP for its activity. If you follow the pathways backward you will see how insulin binding leads to a decrease in cAMP levels, reducing PKA activity, releasing ACC from inhibition, thereby promoting lipogenesis. phosphatidylinositol-3-kinase phosphorylates membrane phospholipids, the major product being phosphatidylinositol-3,4,5-trisphosphate.

Answer 23

PKA inhibits ACC (acetyl CoA carboxylase)

Answer 24

Activates adenyl cyclase Activates PKA Encourages lipogenesis

Answer 25

Counter-regulatory hormones act principally (not exclusively) through activity of PKA, which phosphorylates key enzymes in metabolic pathways Insulin action leads to dephosphorylation of these same enzymes

Answer 26

Type 1: absolute insulin deficiency (due to destruction of insulin-producing pancreatic beta cells) Type 2: variable combination of insulin resistance and insulin insufficiency

Answer 27

Random plasma glucose ≥ 11.1 mmol L-1 Fasting plasma glucose ≥ 7.0 mmol L-1 Oral glucose tolerance test (OGT) ≥ 11.1 mmol L-1

Answer 28

Reduce macro- and microvascular complications Glycosylated Hb (A1C) levels are good indicator of glycaemic control Less than 6.5% is good Every 1% fall in A1C results in 20-30% relative risk reduction in microvascular complications But difficult to do

Answer 29

One of the reasons for that is probably the intricate interplay of insulin, glucagon, and other hormones in healthy physiology. For this reason, in T1DM, insulin dependent, but hard to achieve glycemic control with insulin alone. We’ll take a look at another example of this hormonal interplay,

Answer 30

Evidence for its impairment in T2DM Major target for new drug development Experiment: It involves continuous monitoring of plasma glucose (not shown) as well as insulin. Two sets of measurements. First, you give an oral glucose load and monitor plasma glucose over the course of 2-3 hrs. We know it will rise a bit and we track the time-course and amount of this rise. Second, you repeat, but this time no oral glucose, instead you attempt to copy as closely as possible the previously-measured change in plasma glucose by iv infusion of glucose. In both cases we track the insulin response. The result is a much greater insulin response when glucose enters circulation via the oral route than when the same levels are directly infused into the blood. What do we conclude from this? Something in the GI tract must potentiate insulin release in response to glucose, since insulin release is lower when you by-pass the gut.

Answer 31

The incretins: glucagon-like peptide-1 (GLP-1) and GIP

Answer 32

GLP-1 R activates adelylate cyclase, ↑cAMP, amplifies glucose-induced insulin release Also SU drugs, adrenergic R, muscarinic R, plus others. Insulin injection is too crude to replace this fine detailed level of control.

Answer 33

Metformin: Decreases gluconeogenesis Sulfonylureas: bind and close KATP channels, depolarize B cell releasing insulin Thiazolidinediones: activate PPARγ receptor (controller of lipid metabolism), which (somehow) reduces insulin resistance SGLT2 inhibitors: promote glucose excretion via kidney Incretin targeting drugs: potentiate insulin release in response to rising plasma glucose → DPP-4 inhibitors (prevent breakdown of natural incretins) → Synthetic GLP-1 analogues

Answer 34

TYPE 1: B cell destruction TYPE 2: Insulin resistance/deficiency due to B cell dysfunction

Answer 35

Polyuria Polydipsia Weight loss Random plasma glucose over 11mmol Fasting plasma glucose over 7mmol

Answer 36

``` Diagnosis should not be based on a single glucose sample Two samples on separate days, either: - fasting - random - 2 hour post load ```

Answer 37

Complete lack of insulin | So adipose tissue breakdown and high ketone levels (ketoacidosis)

Answer 38

Hypoglycaemia

Answer 39

Alpha and beta chains altered to make insulin analogues work quicker/slower eg glycine + arginine added to make it more slow acting

Answer 40

To prevent ketoacidosis by mimicking normal insulin levels in non diabetics

Answer 41

10-20 mins Novorapid Humalog Apidra Flasp - 5 mins

Answer 42

Prescribing errors Delivery errors (as in using it wrong) Dispensing errors

Answer 43

Lack of insulin in type-1 diabetes increases blood glucose Glucose has an osmotic effect and causes diuresis, dehydration and circulatory collapse Increase blood levels of Ketone bodies and a condition called Ketoacidosis (DKA) Left untreated leads to death Urgent insulin treatment needed

Answer 44

Never stop insulin and check for ketones Measure BMs 4 times a day If BM < 11 mmol continue normal insulin If BM 11-17 mmol add extra 4 u with meals If BM > 17 mmol add extra 6 u with meals Drink milk, fruit juice, 5 pints sugar free fluid /day If nausea and vomiting and BM >17 call Dr

Answer 45

Missed/delayed meals (e.g. investigations and procedures, waiting for porters, delayed discharge, reduced appetite, food preference) Overdose or mistiming of insulin or SU Weight loss or frailty Increased physical activity, e.g. physio Poor injection technique/ lipohypertrophy Renal or hepatic impairment Other, e.g. heat, alcohol, resolving infection

Answer 46

``` AUTONOMIC Hunger Confusion Sweating Shaking Dizziness Tachycardia ``` Adrenaline and Glucagon release (fight or flight) NEUROGLYCOPAENIC Confusion Drowsiness Discoordination Slurred speech Atypical behaviour (e.g. aggression, irrational reasoning) Severe: reduced consciousness, coma, convultions. impaired cerebral function below 3.5mmol/L

Answer 47

Has glucagon kit | Inject intramuscularly

Answer 48

give glucose 15 – 20 g Recheck CBG 10 – 15 minutes later If still below 4 mmol/L – give glucose again Recheck CBG and document Give slow acting carbohydrate e.g. a sandwich, banana, crackers Analyse cause of hypo and review treatment. Refer to Diabetes Specialist Nurse

Answer 49

Small computerised battery operated pump Pump reservoir – holds 2-3 days worth of insulin 1.8ml-3ml Infusion set – thin plastic tube with a soft cannula or steel needle at the end. This is inserted just under the skin. Length 6mm CSII eliminates a large subcutaneous insulin depot of the BG insulin

Answer 50

Type 2 diabetes is traditionally treated in a stepwise manner. Initial therapy is usually diet and increased exercise. However, lifestyle measures generally fail to control glycaemia and, therefore, pharmacological treatment is instigated. Initial therapy is with a single oral drug although monotherapy often fails over a period of time and a combination of two or more oral therapies is used. Subsequently, failure of all oral combination therapy may occur when -cell failure has progressed to such a degree that additional, exogenous insulin is required

Answer 51

``` Biguanides- Metformin Sulphonylureas Glitazones Alpha-glucosidase inhibitors- Acarbose GLP-1 analogues (Subcutaneous) DPP-IV inhibitors SGLT2 inhibitors Insulin ```

Answer 52

First line treatment in type 2 Reduces Hepatic glucose output Reduces Fatty acid oxidation Increase kinase activity of insulin receptor Increases translocation of GLUT-4 transporter Increases glycogen storage

Answer 53

``` Stimulate insulin secretion Potent Act on beta-cells Closes ATP dependent K+ channels Results in Ca2+ influx and release of insulin storage granules ``` Blocking of K+ATP Channels (as does Glucose)

Answer 54

sharp difference between the insulin response to oral glucose compared with the response to intravenous glucose = incretin effect. Plasma glucose levels are shown in the left panel. The right-hand panel shows the insulin response as measured by C-peptide (a surrogate marker for insulin). On the left, the blue line demonstrates plasma glucose levels achieved in response to an oral glucose load. The blue line on the right indicates the corresponding insulin response. The orange lines demonstrate the plasma glucose and C-peptide responses to intravenous glucose. The difference is the incretin effect, indicated by the shaded area on the right. Subjects received glucose doses of 25, 50, or 100 g dissolved in a standard volume of 400 ml in a random order.

Answer 55

The incretin effect is reduced in patients with type 2 diabetes

Answer 56

Upon the ingestion of food, plasma glucose levels increase postprandially. GLP-1 is secreted from intestinal L cells and provides a stimulus to the β-cells to release insulin in a glucose-dependent manner. When plasma glucose levels return to normal, the action of GLP-1 decreases1. GLP-1 also suppresses glucagon levels that are inappropriately elevated in patients with type 2 diabetes. Lower glucagon levels leads to decreased hepatic glucose output In the stomach, GLP-1 slows the rate of gastric emptying, which reduces the rate at which meal-derived glucose appears in the circulation In the brain, GLP-1 promotes satiety and reduces appetite, which leads to a feeling of fullness and a reduction in food intake All these actions help maintain overall glucose homeostasis.

Answer 57

GLP-1 (Glucagon-like peptide-1) GIP (Gastric inhibitory polypeptide)

Answer 58

Synthetic version of salivary protein found in the Gila monster More than 50% overlap with human GLP-11 Binds GLP-1 receptors on β-cells (in vitro) Resistant to DPP-IV inactivation3

Answer 59

Exenatide Liraglutide Lixisenatide

Answer 60

Alogliptin Sitagliptin Liagliptin Saxagliptin

Answer 61

Oral tablets

Answer 62

Dapagliflozin Canagliflozin Empagliflozin A novel insulin-independent approach to remove excess glucose- work on nephron to increase urinary excretion of glucose (UTI is a possible side effect)

Insulin and Diabetes Flashcards

(86 cards)