diabetes management
DESCRIPTION
its made from harrisonTRANSCRIPT
![Page 1: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/1.jpg)
Management of Diabetes mellitus
Dr. Kartik Doshi 25.1.2012
![Page 2: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/2.jpg)
Overview
• Learning Objectives
• Introduction
• Disease burden
• Physiology
• Pathogenesis
• Management of type 1 DM
• Management of type 2 DM
• Recent advances
• Summary
• References
![Page 3: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/3.jpg)
Objective
• Types and pathogenesis of DM
• Signs, symptoms and laboratory investigations
• Management of type 1 and type 2 DM
• Recent advances in DM management
![Page 4: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/4.jpg)
• In 1869 , German medical student – Pancreas has two
distinct group of cells.
• Frederick Banting. J j r Macleod. Charles Best. J b Collip.
• Indian physician ( charak and sushruta ) – “mudhumeha”
History
PAUL LANGERHANS
![Page 5: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/5.jpg)
1921 – Banting and Best
![Page 6: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/6.jpg)
![Page 7: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/7.jpg)
Introduction
• Definition *
Diabetes mellitus is a group of metabolic
disease characterized by hyperglycemia
resulting from defect in insulin secretion,
insulin action or both.• 246 million worldwide• Prediabetes – great concern
*American diabetic association (ADA) Diabetic Care 28:2005
![Page 8: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/8.jpg)
Spectrum of glucose homeostasis and DM
Source :Harrison 18E
![Page 9: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/9.jpg)
![Page 10: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/10.jpg)
Physiology of glucose metabolism
![Page 11: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/11.jpg)
Regulation of insulin secretion
![Page 12: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/12.jpg)
Phases of insulin secretion
![Page 13: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/13.jpg)
Insulin – tissue level
![Page 14: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/14.jpg)
Pathophysiology of DM
![Page 15: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/15.jpg)
Signs and symptoms • Polyurea – osmotic diuresis • Polydypsia• Weight loss – catabolic state• Fatigue • Weakness• Frequent superficial infections• Blurred vision • Look for complications
![Page 16: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/16.jpg)
Physical examination Weight / BMI Injection sites
Retinal examination Vibratory sensation
Foot examination Tooth examination
Orthostatic blood pressure
Peripheral pulses
![Page 17: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/17.jpg)
Diagnosis*Symptom of DM + RBS (Random Blood Sugar)
> 200mg/dl
FBG (Fasting Blood Glucose)
> 126mg/dl
HbA1C (glycosylated Hb) > 6.5%
PPG (OGTT – 75 gm anhydrous glucose)
> 200mg/dl
PPG – post prandial glucose *ADA- American Diabetic Association
![Page 18: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/18.jpg)
Categorize into types
Type 1• Age < 30 years • Lean body habitus • Autoimmune attack on β
cells or idiopathic • Require insulin as therapy• DKA• Other autoimmune
disorders
Type 2• Age >30 years• 80% obese, can be lean• Insulin resistance, relative
insulin deficiency• OHAs + insulin• HHS, type 2 DKA prone • Component of metabolic
disorder• LADA – latent autoimmune
diabetes of adult
![Page 19: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/19.jpg)
Laboratory assessment
FBGPPBGGlycosylated Hb (HbA1c )SMBG ( self monitoring of blood glucose) Lipid level TFT Urine for protein Stress testing (in high risk pt.)
![Page 20: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/20.jpg)
Advantages of HbA1C Testing Compared With FPG or 2HPG
for the Diagnosis of Diabetes
Standardized and aligned to the DCCT/UKPDS
Better index of overall glycemic exposure and risk for long-term complications
Substantially less biologic variability
Substantially less pre-analytic instability
No need for fasting or timed samples
Relatively unaffected by acute perturbations in glucose levels
![Page 21: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/21.jpg)
Treatment goals for diabetic adults
Glucemic control
A1c < 7.0%
Pre-prandial capillary plasma glucose
70-130mg/dl
Peak post prandial plasma glucose
<180mg/dl
BP <130/80
Lipids (LDL) <100mg/dl
![Page 22: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/22.jpg)
Comprehensive diabetes care
patient
nutritionist
specialists
DM educator
Endocrinologist
![Page 23: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/23.jpg)
Interlocking ideas
Exercise
Nutrition
Diabetes educatio
n
![Page 24: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/24.jpg)
Monitoring level of glycemic control
• Short term – SMBG complimentary• Long term – HbA1c to each other
• SMBG 3-4 times/day (pt. taking multiple insulin)Site – fingertip• CGMS (continuous glucose monitoring system)• Ketone bodies – β hydroxybuterate in blood• Fructosamine assay - hemoglobinopathies
![Page 25: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/25.jpg)
Management Type 1 DM
• Partially or completely lack insulin
• INSULIN replacement is essential
• Basal, exogenous –prevent glycogen breakdown, gluconeogenesis
• Meal time – glucose uptake and storage
![Page 26: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/26.jpg)
What are the types of insulin regimens?
• Premixed regimen
• Split mix regimen
• Basal bolus regime (multidose)
• Bedtime dosing alone (detemir/Glargine)
• Infusion
![Page 27: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/27.jpg)
Premixed insulin Advantages • More accurate dosing • Lesser injections • Pen devices administer premixed forms
Disadvantages • Fine tuning may not be possible• Strict meal pattern• Nocturnal hypoglycemia• May need “diet changes for insulin” rather than “insulin
changes for diet”
![Page 28: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/28.jpg)
Split-mixed insulin
Advantages • Less hypoglycemia, with fine tuning• More physiologic• Adjustable meal pattern
Disadvantages • More patient education required• Cumbersome mixing• Pen device not feasible if two injections are planned
for.
![Page 29: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/29.jpg)
Insulin dosage
0.5-1unit/kg per day in divided doses
• 50% - basal insulin • Insulin – sensitive to heat and O2
![Page 30: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/30.jpg)
Insulin regimes
![Page 31: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/31.jpg)
Cont…
![Page 32: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/32.jpg)
cont…
B – breakfastL – LunchS –SupperHS – nightNPH – Neutral protein hagedon
![Page 33: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/33.jpg)
CSII
![Page 34: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/34.jpg)
![Page 35: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/35.jpg)
Hypoglycemic drugs in Type 1 Dm
Pramlinitide Amylin analogue, given before meal 15µg start – up to 30-60 µg Reduce gastric emptying, Glucagon ↓
Acarbose Alpha glucosidase inhibitor Reduce absorption of glucose Hypoglycemic reaction – Rx Glucose
![Page 36: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/36.jpg)
Diabetic ketoacidosis
• Diabetic coma • Its an emergency!!!• s/s – nausea, vomitting,
thirst, polyurea• PPt. events• Insulin ↓,glucagon↑↑• Hyperglucemia, ketosis,
acidosis, hyperkelemia, hyponatremia
![Page 37: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/37.jpg)
Point to remember
DKA
Always treat in emergency/ICU setting in initially 24-48 hours.
![Page 38: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/38.jpg)
Confirm diagnosis (plasma glucose, serum ketones, metabolic acidosis)
Assess : serum electrolytes, acid base status, RFT
Replace fluids, 2-3 L of 0.9% saline over 1-3 hrs(15-20ml/kg/hr), 0.45% saline at 250-500ml/hr.
Short acting insulin IV(0.1units/kg) f/b infusion 0.1units/kg/hr, ↑es 2-4hr- no response
![Page 39: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/39.jpg)
Monitor following measures
• Assess ppt factor – CXR, culture, USG• Capillary glucose 1-2 hrly• Acid-base status and e - 4 hrly for 24 hr• BP, pulse, respiration, mental status, Urine
input-output 1-4 hrly• Measure K+ every 1-2 hourly• Measure PO4• ECG
![Page 40: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/40.jpg)
Hyperglycemic hyperosmolar state (HHS)
• Elderly person type 2 DM• Several week H/O polyurea, weight loss, • Hypotension, tachycardia, altered mental
status• Relative insulin deficiency and fluid intake ↓• Glucose – 1000mg/dl, osmolarity >350mos/l• Prenatal azotemia• Mortality – 15%
![Page 41: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/41.jpg)
Treatment of HHS
• Fluid balance
Start with 0.9% NS 1-3L over 1-3 hr Fast Repletion of fluid – neurological dysfunctionNa > 150meq/l - 0.45% NS useHemodynamic stability – 0.5 % dextrose useGlucsoe – insulin infusion after glucose 250mg/dl Insulin – same as DKA
![Page 42: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/42.jpg)
Type 2 DM
![Page 43: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/43.jpg)
Food and exercise
• Medical nutrition therapy
• Glycemic index ( GI)• 150 min/wk (atleast for
3 days)• Type 2 – resistance
training• Exercise – can lead
hypo/hyper- glycemia • Pre/inter/after exercise
glucose testing
![Page 44: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/44.jpg)
The economic driving factors……
Adam Drewnowski and SE Specter. Poverty, obesity, and diet costs. Am J Clin Nutr 2004;79:6 –16
> Rs. 70/- per kg
Rs. 90/- per kg
…Consumer Price Index shifts favour unhealthy products
![Page 45: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/45.jpg)
Drug options
• Sulfonylureas • Meglitinides• Metformin
• Thiazolidinediones• α- glucosidase inhibitors
• Peptide analogues • DPP4 inhibitors
• Insulin
![Page 46: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/46.jpg)
Different site actions of OHAs
AGI,Pramlinitide
Incretins , SU,Meglitnides
MetforminTZD
![Page 47: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/47.jpg)
Pharmacotherapy of type 2 DM
LIFE STYLE MODIFICATION
A1c 6.5-7.5 A1c 7.5 - 9 A1c >9
MonotherapyMet/ TZD/DPP4 inh./AGI
Dual therapy
Triple therapy
Insulin / insulin agonist
Drug naïve Under treatmentSymptom free
Symptom +nt
Insulin /insulin agonist
No response – after at least 2-3 months therapy
![Page 48: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/48.jpg)
• Mono therapy • Dual therapy
• Triple therapy
Met DPP4/ GLP 1, TZD, Glinide/SU
TZD DPP4/GLP 1Met Colesevalam, AGI
Met + GLP 1 or DPP4 TZD
SU or glinide
![Page 49: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/49.jpg)
Monotherapy for HbA1c 6-7.5%
• Metformin (insulin sensitizer) – 1st choice• Except,1. Renal disease2. Hepatic disease3. GI intolerance 4. Lactic acidosis• Secretogogues –not preferred
![Page 50: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/50.jpg)
Cont…
• TZD – take time to act, remains for long time, associated with bone fractures
• Use : metabolic syndrome, NAFLD • Proceed to next step – after max. dose for
adequate duration
![Page 51: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/51.jpg)
Dual therapy
• Metformin – preferred for 1st line for dual therapy
• TZD – after metformin preferred ( central drug for combination)
• Met > TZD,• Incretin mimetic > DPP4 inh. > Glinides > SU• GLP-1 analogue – meal induced glucose
excursion , weight loss
![Page 52: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/52.jpg)
• Glinides – more helpful in meal induced glucose ↑ ( HbA1c 7.5%)
• Standard dual therapy – met + TZD• Other regime Metformin + colesevalam (safe, LDL ↓es)Metformin + AGI (anti- atherosclerotic actions)
![Page 53: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/53.jpg)
Triple therapy
• 6 options available • Metformin 1st agent unless CI• Exenetide – 2nd agent ( or DPP4 inh.)• Exenetide – CI ( pancreatitis)• 3rd agent – glinides/TZD/SU
![Page 54: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/54.jpg)
Insulin
• Reason – no b cell reserve • Can be combined with OHAs • Most useful – metformin • Can be with TZD ( CHF)• 3 regime 1. Basal insulin ( glargine )2. Pre mixed insulin ( 2 injections )3. Basal + bolus (4 injections)
![Page 55: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/55.jpg)
HbA1c 7.5-9%
• Start with dual therapy• Metformin – 1st agent • Combinations 1. Metformin + GLP1 analogue2. Metformin + DPP4 inh.3. Metformin + TZD ( wt. gain, edema)4. Metformin + SU ( more glucose lowering
action require)5. Metformin + glinides
![Page 56: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/56.jpg)
Triple therapy
• Same as above category • Differences 1. No use of glinides, AGI, colesevalam 2. Metformin +TZD +SU – weight gain, edema,
hypoglycemia• Insulin – same as above • Discontinue ≥1 OHAs• Incretins + insulin – NOT APPROVED
![Page 57: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/57.jpg)
HbA1c >9%
• Triple therapy• Insulin – should give drug naïve patients• SU – give importance Faster actionRobust Glucose lowering effect• Insulin – gradually discontinue after
HbA1c<6.5%• Give dual/triple therapy
![Page 58: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/58.jpg)
Insulin in type 2 DM
DM – not controlled with max. dose (metformin – 2500mg/day)
Physiological stress, infection Use of parentral nutrition/high caloric dietDKA/HHSGestational DMCRFProgressive complication (D. retinopathy)
![Page 59: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/59.jpg)
Selection of drugs
Level of hyperglycemia – choice of initial therapyMild – moderate DM (200-250 mg/dl) – often
respond to monotherapyMore rapid glucose control – glucose toxicity ↓↓Fast control – AGI and Insulin secretogoguesNo single agent – distinct advantageTZD – target basic problem in type 2 Cost effective – metformin, SU
![Page 60: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/60.jpg)
Combination therapy
• Same dose as monotherapy• Different M/A – So additive• Eg. SU and Metformin
• Insulin + TZD – more chances of hypoglycemia, weight gain
![Page 61: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/61.jpg)
CIs of combination therapy
× Complicated DM× DM with sepsis× DM with tissue hypoxia and systemic BP less
then 90 mm of Hg× Type 1 DM× DKA× DM with pregnancy× Auto immune DM
![Page 62: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/62.jpg)
Pharmacological agents
Bigunides - Metformin, phenformin
Most commonly used drug M/A – AMP Protein kinase
HGP ↓, peripheral utilization
500mg -1000mg bd/day
![Page 63: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/63.jpg)
Mechanism of action
![Page 64: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/64.jpg)
Alpha glucosidase inhibitor
• Acarbose, vogliboseDose – 25 mg evening meal – 50-100mg/every
meal (acarbose)Hypoglycemia – glucose as a treatmentAdditional actions Anti atherosclerotic Anti platelet Decrease fibrinogen, inflammation Cardio protective in IGT patients
![Page 65: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/65.jpg)
Insulin secretogogues
Sulfonylurease
Meglitinide analogues
Glucose , AA
GLP-1 receptor agonist
DPP4 inhibitors
![Page 66: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/66.jpg)
K+K+
140 kDa140 kDa
65 kDa65 kDa
- cell membrane - cell membrane
K+K+
KATP channelKATP channel
Modes of action: Glimepiride (SU) Most Sulphonylureas
Glimepiride
Sulphonylurea
Receptor
65kDa Component absent in Cardiovascular System
Safer to use in patients with a higher cardiovascular risk
So What ??
Glimepiride
GLUT-4
![Page 67: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/67.jpg)
Incretins
• Entero- insular axis / entero-hypothalamo-insular axis
• GIP – glucose dependent insulinotropic peptide
• GLP 1 – glucagon like peptide• Preserve B cell mass• Synthetic incretins – use as a drug• “Incretomimetic” and “incretin enhancer”
![Page 68: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/68.jpg)
Incretin hormones
GLP-1 receptor agonist• Secreted by L cells • Stimulate – glucose induced• Effect on glucagon • Delay gastric emptying
• Circulating level of GLP-1 reduced
• Enhance B cell proliferation• Eg. Exenetide, liraglutide
GIP • Secreted K cells• Stimulate – glucose induced• No effect on glucagon • Does not delay gastric
emptying• Circulating level GIP are
normal/high• Same effect• None
![Page 69: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/69.jpg)
GLP – 1 secretion and metabolism
LOWERING OF BLOOD GLUCOSE
INCRETIN GLP -1
DPP – 4 ENZYME INACTIVATES GLP-1
• INHIBITS GLUCAGON
RELEASE
STIMULATES INSULIN
RELEASE
DPP-4 INHIBITORS (DRUGS) BLOCK DPP-4 AND DECREASE
GLUCOSE
![Page 70: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/70.jpg)
![Page 71: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/71.jpg)
Doses Metformin 0.5-2.5gm 2-3 doses/day
Glimipiride 1-6mg 1
Pioglitazone 15-45 mg 1
Nateglinide 180-480mg 3-4 doses/day
Exenetide (SC) 10-20µg 2 doses/day
Sitagliptin 100mg 1
![Page 72: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/72.jpg)
Recent advances
![Page 73: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/73.jpg)
Cont…
Oral insulin – physiological insulin Use – Ecuador ( india – biocon )
Cortisone Cortisol (active) Enzyme – 11-B hydroxysteroid dehydrogense Activators of glucokinaseStatins – pravastatin (most useful)
![Page 74: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/74.jpg)
Molecular size correlates with rate of absorption
Monomer
Hexamer
Multi-hexamers
Molecular size
Dura
tion o
f A
ctio
n
Di-Hexamer
![Page 75: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/75.jpg)
Capillary membrane
Subcutaneous tissue
Insulin degludec in blood Albumin binding
Monomers
Insulin degludec: Mechanism of protraction
Cell Membrane
Capillary blood
Insulin Receptors
Multi-hexamers
![Page 76: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/76.jpg)
Gestational and other DM• Intensive treatment required • Fetal macrosomia • Insulin only is used• 30-60% - chance of type 2 DM
Pediatric DM• More chances – hypoglycemia, coma • Metformin – only approved (10mg/ml)
![Page 77: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/77.jpg)
Prediabetes : What’s in a Name?
Use for IGT and IFG If 50% chance of DM – next 10 yearsForerunners of DM, CV riskLife style modification and metformin*
1. <60 years of age2. BMI >35kg/m2
3. Family history4. TG, HDL5. HT6. A1c > 6.0%
![Page 78: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/78.jpg)
References
• Harrison 18th edition • Goodman and gillman. Pharmacological basis
of therapeutics. 12th edition• KDT 6th edition • Medicine update 2008. Vol.18• An algorithm for glycemic control. AACE/ACE
consensus statement. Endocr Pract. 2009;15(No. 6)
![Page 79: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/79.jpg)
INSULIN
SECRETAGOGUES K+ATP
SULFONYLUREAS
1st – Acetohexamide, Tolbutamide, Chlorpropamide, Tolzamide.
2nd – Glibenclamide, Glipizide, Gliclazide
3rd – Glimepiride
MEGLITINIDES/ PHENYLALANINE
Nateglinide, Repaglinide
GLP -1 ANALOG
Exenatide, Liraglutide
DPP IV INHIBITORS
Sitagliptin, Vildagliptin, Saxagliptin
SENSITIZERSBIGUANIDES Metformin
TZD (PPAR) Rosiglitazone, Pioglitazone
OTHERSα - GLUCOSIDASE INHIBITORS
Acarbose, Miglitol, Voglibose
AMYLIN ANALOG Pramlintide
Summary
![Page 80: Diabetes management](https://reader033.vdocument.in/reader033/viewer/2022060111/5562666dd8b42a14048b5055/html5/thumbnails/80.jpg)
Thank you