This document discusses diabetes mellitus and provides information on investigations used to diagnose both type 1 and type 2 diabetes. It describes tests such as urine glucose, blood glucose levels, HbA1c, and c-peptide that can indicate diabetes or prediabetes. Diabetic ketoacidosis, a medical emergency, is also summarized, including its metabolic disturbances, clinical features, and management through fluid resuscitation and insulin administration. The document outlines the pathophysiology and risk factors for both type 1 and type 2 diabetes.

1. Diabetes Mellitus
Brig(Dr) A B Khare (retd)
Associate Professor (med)

2. Diabetes Mellitus
• Investigations ;
1. Urine glucose
2. Blood glucose : venous plasma glucose
Diabetes :- fasting> 126mg% ,2 hrs after 75 gms glucose or
random sample>200mgm% ,hba1c >6.55%
Pre diabetes :- ifg >110 -<126mgm% ,igt 2hrs after 75 gms
glucose 140-200MGM%

3. Diabetes Mellitus
• Interstitial glucose :- CGM systems – tiny sensor under skin , life -2 weeks
,measures every 1-5 min.
• Urine & blood ketones :- identified by nitroprusside reaction in urine.
Also found in fasting , strenuous exercise , repeated vomiting , diet high fat
low carb. Major ketone β-(OH)BA found in blood during DKA detected by
stick/electronic meter . useful for management & prevention in DKA.
• Glycated haemoglobin :- accurate & objective measure of glycaemic
control over weeks to months. On enzymatic covalent attachment of
glucose to Hb.

4. Diabetes Mellitus
• Islet antibodies :- high titre islet antibodies suggest type 1DM.
Antibodies against components – insulin , glutamic acid
decarboxylase , protein tyrosine phosphatase –related proteins (ia-2)and Zn
transporter ZnT8.
• C-peptide :- marker for endogenous insulin
• Urine proteins:-microalbuminuria indicator of diabetic nephropathy/risk of
macrovascular disease.

5. Diabetes Mellitus
• Aetiopathogenesis :- in both types interplay of environmental factors with
genetics decide who &when.
• Type 1 dm :-
Autoimmune destruction of beta cells based on model –G. Eisenborth
Genetically susceptible individual exposed to environmental trigger
 Beta cell autoimmunity progressive loss of beta cells.
Initially fast first phase insulin secretion loss - IGT & undiagnosed DM
• Pathology– inflammatory lesion ‘insulitis’- β cell specific.
Molecular mimicry, oxidative stress, viral infection
Autoab-20-25%-single type,50-60% double , 70%threetype.

6. Diabetes Mellitus
• Genetic predisposition–
Strong but complex
Multifactorial
Monozygotic twins 30-50% concordance
Dizygotic 6-10%
Inheritance polygenic -20 regions in human genome
HLA region - MHC short arm chromosome 6

7. Diabetes Mellitus
• Environmental predisposition –
wide geographical &seasonal variation &rapid acquisition in migrants.
Nature of environmental factor – 1-viruses , 2- food , 3- bovine serum albumin
4-vit d.
• Metabolic disturbance – present on crossing a threshold β cell destrn. Resulting
High glucose toxic to β cell .Hyperglycaemia—glycosuria—dehydration-fatigue,
polyuria ,nocturia , thirst ,polydipsia

8. Diabetes Mellitus
Unrestricted lipolysis & proteolysis – weight loss
Ketoacidosis – when generation exceeds metabolic capacity
Duration of symptoms – short – few weeks.
• Type 1 DM in adults– presence of islet AB in high titre-- usually Gad antibody
Without rapid progression to insulin therapy. Initially managed as type 2 DM but
Eventually require insulin.

9. Diabetes Mellitus
• Type 2 dm diagnosis of exclusion , highly heterogenous
Initially insulin resistance  increased insulin secretion 
eventual β cell failure.
One group– young – insulin resistance due to obesity ,ethnicity
Second group – old- nonobese –pronounced β cell failure
Key feature relative insulin deficiency

10. Diabetes Mellitus
• Insulin resistance & metabolic syndrome
often have hypertension , dyslipidaemia (high LDL ,TG , low HDL) , NAFLD ,PCOD.
Much more common in obese people
Cause of insulin resistance –
1- central obesity– active adipocyte– FFA – compete with glucose
Adipokine like cytokine – on liver &muscle
receptors –insulin resistance

11. Diabetes Mellitus
2-- physical activity
Inactivity – downregulation insulin sensitive kinase—ffa accumulation
3– deposition of fat in liver – NAFLD – NASH – cirrhosis .
• Pancreatic β cell failure
Early stage modest decrease in β cell mass.
At diagnosis 50%decrease and decline thereafter.
Amyloid deposition
Increased FFA & glucose –toxic effect on β cell—impaired insulin secretion.

12. Diabetes Mellitus
• Genetic predisposition
Monozygotic twins 100% concordance
Over 70 genes/gene regions are associated in β cell function /turnover
&regulation of cell cycle.
Powerful influence by environmental factors.
• Environmental factors
Overeating ,obesity , decreased activity , age (70%>50 yrs) , ethnicity

13. DIABETES MELLITUS
• Metabolic disturbance
Slow onset relative insulin deficiency
In contrast to type 1 lipolysis &proteolysis not unrestrained – wt. loss
&ketoacidosis seldom
hyperglycaemia over years
At diagnosis – asymptomatic , fatigue over many months ± osmotic Sx , some
spiral decline –DKA , ketosis prone Flatbush syndrome

14. Diabetes Mellitus
• Aetiological classification
• Type 1 DM immune mediated , idiopathic
• Type 2 DM
• Other specific types genetic defect of β cell function
Genetic defect of insulin action
pancreatic disease
Excess endogenous antagonist hormone production
Drug induced
Genetic syndromes
• Gestational

15. Diabetes Mellitus
• Presenting problem
Hyperglycaemia ; thirst , dry mouth , polyuria , nocturia , tiredness , fatigue ,
lethargy , change in weight , blurring of vision , pruritus
Vulvae/balanitis , nausea , headache , hyperphagia ,
predilection for sweet foods , mood change , irritability ,
difficulty in concentrating , apathy .

16. Diabetes Mellitus
• Diabetic emergencies
 Diabetic ketoacidosis
medical emergency
Features ; hyperketonaemia > 3.0 mmol/l or ketonuria> 2 +
hyperglycaemia >200 mg %
metabolic acidosis ph. <7.3 or H+ >50 nmol/l

17. Diabetes Mellitus
• Profound osmotic diuresis
• Potassium loss
• Ketosis
• Metabolic acidosis
• Loss of fluid & electrolytes

18. Diabetes Mellitus
• Clinical features ;
loss of skin turgor ,furred tongue ,cracked lips ,tachycardia ,
hypotension , decreased I O P , deep sighing breathing (Kussmaul’s
sign) , sweet smell of acetone , mental apathy , delirium , coma
Abdominal pain
• Investigations (without delaying fluid & insulin administration )
venous blood ;urea ,electrolytes ,glucose , bicarbonate , acid base
Urine & blood samples for ketones
Infection screen ; CBC , C-reactive protein , blood / urine culture chest x ray
Leucocytosis

19. Diabetes Mellitus
• Features of severity ;
blood ketones > 6.0 mmol/l
Bicarbonate <5mmol/l
Venous / arterial blood ph <7.0
H+ >100nmol/l
K+ <3.5mmol/l
GCS <12 h r < 60 or > 100
O2saturation <92%, SBP <90, anion gap >16 mmol/l

20. Diabetes Mellitus
• Management ;
fluids ; isotonic saline (.9% nacl) (correction of ecf )
10 % igs WHEN BLOOD sugar <200mg % (correction of icf)
Insulin ; infusion .1 u/kg /hr
Or
Im loading dose 10-20 u followed by 5 u/hr
Or
Subcutaneous .3u/kg then .1 u/kg
Blood glucose fall 50-110mg% /hr ,ketone conc. By .5 mmol/hr

21. Diabetes Mellitus
• POTASSIUM
• BICARBONATES
• PHOSPHATES
• OTHER ONGOING TREATMENT

22. • TO BE CONTINUED……….