management of diabetes mellitus

1. Diabetes Mellitus
Management
Brig(Dr) A B Khare (Retd)
Asso. Prof (Med)

2. MANAGEMENT
Aim :-- Manage symptoms of hyperglycaemia
Minimise risk of micro &macrovascular complications
Treatment :-- diet , life style modification , oral anti diabetic drugs , insulin ,
comorbidity management
Goal :-- FSL- 90-126mg% , pre meal- 72- 126mg% post meal – 72-144mg%
HbA1C -- 6.5% , 7.5% (with complications)
B.P 140-130/80 , total cholesterol ≤150mg% , LDL <75mg%

5. DIABETES MELLITUS
• Diet – Carb; not > 50% of total energy , sucrose < 10%
Fat; not > 35% (> 11% unsaturated fat)
Salt < 6gms/day
• Exercise – walking , gardening , swimming , cycling
150 min/week ; mod intensity, 75 min/ week; vigorous intensity
Muscle strengthening(resistance) 2 or more days/week
Avoid > 90 min sedentary time

6. DRUG THERAPY
Biguanides ,Sulphonylureas ,Alpha-glucosidase inhibitors , Thiazolidinediones,
Incretin based-DPP4 inhibitors & GLP-I Receptor agonist, Sod & glucose
transporter 2 inhibitors.
Biguanides : First line in T2DM & adjunct in obese T1DM ,
Main side effects : diarrhoea ,abdominal cramps , bloating &nausea
mechanism of action: Insulin sensitiser ,↓ glucose hepatic
production ,↑ glucose uptake
Weight neutral, (Est benefits) ,500-1000 mg/day ,
↑lactic acidosis susceptibility , dose adjusted if GFR↓

7. CONTD…
Sulphonylureas :
Insulin secretagogues , established benefit in microvascular complications.
Glibenclamide, glimepiride, glipizide, gliclazide
Meglitinides – repaglinide & nateglinide
Main side effects ; hypoglycaemia , weight gain
2nd line drug
Max benefit < half max dose

8. CONTD…
Alpha-glucosidase inhibitors :
Inhibits disaccharidase in gut , delays absorption
Acarbose , Miglitol ; taken with meal .
Decrease post meal blood sugar modestly
Combined with sulphonylureas.
Main side effects: flatulence , abdominal bloating , diarrhoea

9. CONTD…
Thiazolidinediones : Glitazones / TZD
Enhance action of endogenous insulin directly &indirectly(adipose cells)
Advantage –no hypoglycaemia
Rosiglitazone &pioglitazone
Main side effect : CVS; MI ,CCF
Beneficial in fatty liver , NASH , insulin resistance

10. CONTD…
Incretin based therapy: – DPP-4 inhibitors , GLP-1 receptor agonists
Incretin GLP-1 ,GIP potentiate insulin secretion , broken down by DPP-4
Effect ↓ in T2 DM.
Gliptins/DPP-4 inhibitors ; Sitagliptin, Vildagliptin , Sax gliptin , Linagliptin.
GLP-1 receptor agonists modified to resist breakdown by DPP-4.
Supraphysiological role – delay gastric emptying, decrease appetite
Exenatide , lixisenatide , albiglutide. Main side effects ; nausea
Combined with basal insulin
Pancreatitis

11. Contd…
SGLT 2 Inhibitors :
Dapagliflozin , Canagliflozin ,
Empagliflozin
Appx 25% of filtered glucose not
reabsorbed from PCT &DCT
Glycosuria  genital fungal
infection, weight loss
35% ↓ cardiovascular mortality,
↓ admission due to CHF

12. INSULIN

13. Insulin
• 1921
• 1980s--- porcine ,bovine , human insulin (regular/soluble insulin)
• Hexamers in SC tissue
• Adding chemical – protamine , zinc
• Insulin structure altered – analogues -- lispro , aspart , glulisine
Glargine ,detemir , degludec
• 100u/ml also200,300 ,500u/ml

14. Insulin
Half life few minutes, removed by liver & kidney
Site –anterior Abdominal wall , upper arms , outer thighs , buttocks
Rate of absorption -- site , depth ,vol of inj . ,skin temp , local massage ,exercise
Complication –hypoglycaemia
Dose --- T1 DM multiple dose/ pump ,T2DM basal alone/OHA , twice daily
• Artificial pancreas ; insulin pump +CGMS
• Transplantation ;pancreas ,SPK ,PAK ,SPLK

15. COMPLICATIONS
• Complications
mortality---large vessel disease –MI ,CVA ,PVD
Accelerated atherosclerosis
Amplifies effects of smoking ,HTN , dyslipedemia
Small vessel disease specific complication –diabetic microangiopathy
Thickening of basement membrane-increased permeability

16. DIABETES MELLITUS
• DIABETIC RETINOPATHY
• DIABETIC NEPHROPATHY
• DIABETIC NEUROPATHY
• DIABETIC FOOT
• ACCELERATED ATHEROSCLEROSIS
AS A RESULT OF LOCAL RESPONSE TO GENERALISED VASCULAR INJURY
;THICKENING OF
CAPILLARY BASEMENT MEMBRANE WITH ASSOCIATED INCREASED VASCULAR
PERMEABILITY.

17. DIABETES MELLITUS
• Eye : cataract– permanent opacification of lens– premature/accelerated,
snowflake
• Diabetic retinopathy: Pathogenesis- vascular endothelial growth factor—
capillary occlusion– increased capillary permeability retinal edema 
angiogenesis
Clinical features microaneurysm—leak fluid & blood—edema ,haemorrhage –
edge lipid ppt(exudate)
Vessels occlude ischaemia  new vessel
Neurovascular –retinal nerve fiber haemorrhage—flame
/cotton wool(soft exudate)
Management -- panretinal photocoagulation
• Diabetic macular edema

18. DIABETES MELLITUS
• Diabetic nephropathy >20 yrs –30% in type 1 dm
Activation of renin angiotensin system
Direct toxic effect—renal inflammation fibrosis
Thickening gbm—microalbuminuria
Dposits in mesangium—nodular deposits
Diagnosis--- microalbuminuria
Management– aggressive reduction of b.P, optimise cvs risk factors

19. DIABETES MELLITUS
• Diabetic neuropathy
Pathology– axonal degeneration myelinated/unmyelinated fibers
Schwan cell basal lamina thickening – patchy demyelination
Symmetrical sensory polyneuropathy
Asymmetric motor diabetic neuropathy
Mononeuropathy
Autonomic neuropathy

20. DIABETES MELLITUS
• DIABETIC FOOT
FOOT ULCER -- TRAUMA --NEUROPATHY
VASCULAR
NEUROISCHAEMIC
CHARCOAT NEUROARTHROPATHY