DIABETES- DR.AKIF A.B

HbA1CVALUE CONDITION<5.6% Normal Hb1AC5.6-6.4% Impaired glucose

tolerance>/= 6.5% Diabetes mellitus

-It tells us about average blood sugar of previous 8-12wks

-Retrospective study

-Best investigation of choice for diagnosing Diabetes Mellitus.

-Good diabetes control = Hb1AC levels <7%

DIABETESFasting 2hrs Post

prandialNormal 60-100mg/dl <140mg/dlImpaired glucose tolerance

100-126mg/dl 140-199mg/dl

Diabetes mellitus

>126mg/dl >200mg/dl

Fasting is defined as no calorie intake for at least 8hr

2hrs post-prandial: an oral glucose tolerance test with 75gm of glucose

1 mmol/lit of blood sugar = 18 mg% of blood sugar

1) A young man has normal blood sugar & normal HbA1C but has glycosuria. Most likely diagnosis is?

A Renal Glycosuria

B Pancreatic insufficiency

C Alimentary glycosuria

D High carbohydrate diet taken in the morning.

Ans. A Renal Glycosuria

Important points:1. Glycosuria + Ketonuria : seen only in diabetes.

2. Only glycosuria (without diabetes) : is seen in a normal young adult, pregnancy, hyperthyroid.(Note: In hyperthyroid it is known as alimentary glycosuria)

3. Only ketonuria : seen in prolong starvation.

4. Renal glycosuria:is a benign condition, found in some young adults. No treatment required. Blood sugar is normal. It is self limiting.

TYPE-1 DIABETES- Ratio of type I & type II diabetes in India. = 5% : 95%

-Patient has normal Weight or under weight

- Presence of autoantibodies: islet cell antibodies (lCA) and anti-glutamic acid decarboxylase (GAD) antibodies;

- Ketonuria on urine dipstick.

- Family history +/-

- Serum insulin levels are low

- HLA DR3, DR4

- Main treatment is insulin.

SCHMIDT SYNDROME OR POLYGLANDULAR FAILURE

SYNDROME)-Autoimmune destruction of more than 80% of beta cells

-Type-1 Diabetes Mellitus

LATENT AUTOIMMUNE DIABETES OF ADULTS (LADA)

- Also known as Type 1.5 DM

- Is a form of Type 1 DM, with slower progression to insulin dependence in later life.

-Initially there is not much need of insulin administration and patient can be managed on hypoglycemic drugs but later in adulthood insulin dependence occurs.

-Since initially it behaves as type 2 DM and later as Type 1DM , It is known as Type1.5DM.

-Patient has over Weight

- No HLA association

- No autoantibodies

-Ketosis is uncommon.

-Non ketotic hyper osmolar coma is common.

-Family history strongly positive but not always positive.

- Insulin resistance is the main cause

- Serum insulin levels are very high ( hyper insulinemia )

- Treatment include weight loss, oral drugs & insulin

TYPE-2 DIABETES

2.Q. A 29 years old person is known diabetic on oral hypoglycemic agents since 3 years. He has lost weight and never had DKA. His grand father is diabetic but his father is nondiabetic. Which is the likely diagnosis: (AIIMS May 09)

A MODY

B DM type I

C DM type II

D Pancreatic diabetes

Ans. C. DM type II

3.Q. A 29 years old person is known diabetic on oral hypoglycemic agents since 3 years. He has lost weight and never had DKA. His grand father and father both are diabetic. Which is the likely diagnosis: (AIIMS Nov 09)

A )MODY

B )DM type I

C)DM type II

D ) Pancreatic diabetes

Ans. A MODY

In type II diabetes there is strong family history but in MODY there is definite family history because it is autosomal dominant.

That’s why the answer of Q. 2 is C and

answer of Q 3 is A.

Because in Q. 2 Father is not diabetic but Grand Father is diabetic but

Q. 3 both Father and Grandfather are diabetic.

MATURITY ONSET DIABETES OF YOUNG (MODY)

-Age of presentation = 25yrs

-6types (Type1-6)

-MC MODY in India = Type-3

-No antibodies

-No obesity

-DKA uncommon

-No insulin resistance

-Gene defect = HNF1

-Autosomal Inheritance

-Family history of sucessive generations

Remember Gene names……chromosome names not required.

4.Q. Acute fulminant diabetes is related to:

A) DKA

B )Viral infection

C ) MI

D ) Pregnancy

B )Viral infection

5.Q. Patient of which of the following type of diabetes is most likely to have normal blood sugar?

A Potential

B Latent

C MODY

D LADA

A) Potential

POTENTIAL DIABETES Person himself at present is non-diabetic but has a strong family history of type 2 diabetes.LATENT DIABETES A person becomes diabetic under stressful conditions like pregnancy. Person again becomes non-diabetic when stress is removed.

BRITTLE DIABETES It is seen in children with type 1 diabetes. Some times patient’s sugar becomes very high leading to DKA, sometimes patient goes into hypoglycemia

ACUTE FULMINANT DIABETES MELLITUS It is acute onset diabetes, can occur in any age, occurs after viral infection. Serum insulin level are reduced but there are no antibodies against insulin or beta cell. (PNQ)

The viral infections associated with diabetes are : Mumps, Measles, Coxsackie virus, Cytomegalovirus, Rubella, EB virus

TROPICAL DIABETES-Diabetes mellitus associated with chronic malnutrition and, sometimes, chronic pancreatitis.

-Also called malnutrition-related diabetes.

-Chronic pancreatitis patient are usually in Africa where they consume Casava.

Recent advances in Pathology of Type II diabetes

-Genes for type II diabetics that cause the insulin resistance and the beta cell failure- a gene on chromosome 2 encoding a cysteine protease, calpain –10, has been reported in some patient.

- Several adipokines, secreted by fat cells, can affect insulin Action.

-Example of adipokines 1. Leptin 2. Adiponectin 3. TNF 4. Resistin

i. Adipokines which reduce insulin resistance - a. Leptin b. Adiponectin.ii. Adipokines which increase insulin resistance – a. TNF-alpha b. Resistin

INITIAL MANAGEMENTOF DIABETES

Treatment of diabetes mellitus (H-18th Pg-2990)1. Patient Education : For any obese type II diabetic patient initial

therapy is diet therapy and exercise.

(a) (Reduce weight to maintain normal BMI)BMI = body weight (kg) / height in meters2

BMI > 25 overweight30 obese

(b) In Obesity down regulation of insulin receptors occurs.

(c) Avoid food of high glycemic index (i.e. any food like sugar, glucose powder etc. which are absorbed immediately in GIT and raised blood sugar very fast).

100% Glucose

80-89% Corn Flakes, carrots, potatoes (mashed), maltose, honey, idli.

70-79% Bread (whole meal), millets, rice (white), broad beans, potato (new), uppama

60-69% Bread (white), paratha (Wheat), rice (brown, unhusked), shredded wheat, beetroot, banana, raisins, sprouted green gram, sucrose.

50-59% Buck wheat, noodles (white), peas (frozen), pongal sweet corn, potato chips.

40-49% Noodles (whole mal), porridge oats (dahlia), beans, potato (sweet), oranges (juice), peas (dried), bengal gram, black gram.

30-39% Black-eyed peas, apple, skimmed milk, curd/yogurt, tomato soup, ice cream

20-29% Kidney beans, lentils (all daals), fructose, rajmaah

10-19% Soyabeans, groundnuts

GLYCEMIC INDEX

Q.Which adipokine reduces in insulin resistance

A Leptin

B TNF alpha

C Resistin

D All of the above

A. Leptin

Complications Of DM1) Somogyi phenomenon

2) Dawn phenomenon

3) Diabetic Ketoacidosis

4) Non-ketotic hyperosmolar coma

5) Diabetic retinopathy

6) Diabetic neuropathy

7) Diabetic nephropathy

1)SOMOGYI PHENOMENON-Early morning (3-4am) hypoglycemia due to excess administration of Insulin at night but again at morning around 6-7am there will be hyperglycemia.

Explanation of 6am hyperglycemia is given below

When the blood glucose level falls below normal, the body responds by releasing the endocrine hormone glucagon as well as the stress hormones epinephrine, cortisoland growth hormone. - Glucagon facilitates release of glucose from the liver that raises the blood glucose immediately, and - the stress hormones cause insulin resistance for several hours, sustaining the elevated blood sugar.

1)SOMOGYI PHENOMENON

1)SOMOGYI PHENOMENONNormal glucose at night

High Insulin given at 9pm

Leads to hyperglycemiaIn morning

Glucagon and other stress hormones are released

Due to hypoglycemic stress

Leads to hypoglycemia At around 2-3pm

DAWN PHENOMENON

-Early morning Hyperglycemia at around 2-3am

- Due to low dose administration of Insulin

DIABETIC KETOACIDOSISDiabetic ketoacidosis

Lactic acidosis

Non ketotic hyperosmolar coma

pH Low <7.3 Low <7.3 Normal

HCO3- LOW LOW Normal

Urine ketones +++ -ve -ve

Blood sugar >300mg% >300mg% >800mg%

DIABETIC KETOACIDOSISCLINICAL FEATURES –

Symptoms – Nausea, vomiting, Abdominal pain Altered mental function. Shortness of breath

Signs –1. Tachycardia2. Dry mucous membrane3. Dehydration4. Hypotension5. Kussmaul respiration Q

6. Tachypnea7. Abdominal tenderness8. Fever. May be there9. Fruity odour of the breath

INVESTIGATIONS Of DKA1. Hyperglycemia – Blood sugar 400 – 600 mg%

2. TLC – Leucocytosis. It is a feature of DKA. It does not indicate infection. Presence of fever indicate infection

3. K+ - increase (shifting of K+ from intracellular to extracellular compartment due to decrease Insulin)

4.S. Osmolality 300 – 320mosm/Kg5.Urine ketones – Positive

6. Metabolic acidosis - Low HCO-3

7. increase anion gap.

Q. Which of the following is the best parameter to know about the control of DKA?

A Random blood sugar

B pH of the blood

C Urine ketone

D Serum potassium

B) pH of the blood

Treatment Of DKAa. Fluids → 0.9% saline.

b. Insulin → Regular Insulin is given I/V in DKA. It is not given subcutaneous.

c. Treat precipitating events → Non compliance, infection by antibiotics.

d. K+ replacement → Initially when patient comes initially he is hyperkalemic, later on when patient is treated with insulin, serum potassium level goes down and may required potassium replacement.

e. Injection HCO3 I/V if Ph <7Note : Insulin causes movement of K+ from ECF to ICF leading to hypokalemia

For Pg entrance this is enough ….if u want to know more about management read in harrison/ davidson latest edition

Q. A diabetic patient with blood glucose of 600 mg/dL and Na 122 mEq/L was treated with insulin. After giving insulin the blood glucose decreased to 100 mg/dL. What changes in blood Na level is expected? (LQ)

A Increase in Na+ level

B Decrease in Na+ level

C No change would be expected

D Na+ would return to previous level spontaneously on correction of blood glucose.

Ans. A Increase in Na + level

In diabetes pseudohyponatremia occurs i.e. the measured serum sodium is reduced as a consequence of the hyperglycemia.i. There is a reduction of (1.6 meq) of serum sodium for each 100 mg/Dl rise in the serum glucose.ii. A normal serum sodium in the setting of DKA indicates a more profound water deficit.So when we treat a case of DKA, as the blood glucose level falls then measured serum sodium rises.(Ref. Harrison, 18th edition, 2978)

Extra Edge::Causes of pseudohyponatremia:1. Severe hyperglycemia (DKA, NKHOC)2. Hyperlipidemia3. Hyperproteinemia (Multiple myeloma)

Complications of DKAi. Cerebral edema (most dangerous complication, seen mostly in children)

ii. Venous thrombosis

iii. ARDS

iv. MI

v. Acute gastric dilatation

Acidosis leads to damage of blood brain barrier and thus leads to cerebral edema

Q. Mr. Ram Lal, 80 years, a known case of diabetes, was brought to emergency ward in unconscious state. His blood sugar was 900 mg%, dry tongue. BP; 80/50. Urine ketones negative. Which of the following fluid you will give to treat his marked dehydration.

A Injection RL

B Injection N/2 saline

C Give plain water by Ryle’s tube

D Injection N saline

Ans. D Injection N saline This is a case of NKHOC. Ideal replacement fluid in this condition N/2 saline but in this case the patient BP is 80/50 i.e. he is in hypovolemic shock so to begin with in this case N saline should be given.

Once the systolic BP is above 90mmHg then N/2 saline should be started.

Supposed in this question patient’s BP was 110/70 i.e. normal BP than best answer would have been N/2 saline.)

Q. A 70 years old patient was brought to emergency ward in a comatose state. His ABG was done and findings are as follows Na = 132 meq/lit, K = 6.5 meq / lit, HCO3 = 10 meq/ lit, blood glucose 20 mmol/litBUN = 4 mmol/litWhat is your diagnosis. (AIIMS Nov 09)

A Non ketotic hyperosmolar diabetic coma

B D.K.A

C Hypoglycemic coma

D Lactic acidosis

Ans. D Lactic acidosis In this case the RBS is 20mmol/lit i.e. 20 X 18 = 360 mg%. So this is not a case of hypoglycemia.

Here in this question HCO3 is 10meq/lit so it is not a case of NKHOC.

So because this case has metabolic acidosis either it is a case of DKA or lactic acidosis.

But as patient age is 70 years it is more likely to be lactic acidosis.

Supposed in this question patient age was 17 year than the answer was DKA !!!)

Normal HCO3 levels = 22-26meq/l

LACTIC ACIDOSIS-Lactic acidosisis characterized by low pH in body tissues and blood.

-Lactic acidosis is characterized by lactate levels >5 mmol/L and serum pH <7.35.

-It is very common in type 2 diabetic patient who are on metformin therapy.

-Associated with Vitamin b1 deficiency

-Signs: a. Deep and rapid breathing b. Vomiting c. Abdominal pain.

Treatment:1. Lactic acidosis is typically associated with tissue hypoperfusion. Appropriate measures include treatment of shock, restoration of circulating fluid volume, improved cardiac function, identification of sepsis source2. Sodium bicarbonate is given I/V3. Thiamine

NON KETOTIC HYPEROSMOLAR COMA

(NKHOC)Symptoms –Classically patient isi. Elderlyii. H/O polyuria of several weeks with weight loss and decrease oral intake.iii. Mentally confused

Signs –a. Tachycardiab. Hypotensionc. Dehydrationd. Altered sensorium, coma

Extra Edge:Nausea, Vomiting, Abdominal Pain, Kussmaul respiration & Ketosis are not the features of NKHOC.

Investigation of NKHOC a. Blood sugar 900 – 1100 mg/dl

b. Serum osmolality > 350mosm/kg

c. Pseudo hyponatremia

e. pH normal i.e. no acidosis

f. Ketonuria is absent. i.e. no ketosis

Treatment of NKHOC1. Fluid → Total fluid deficit (9 – 10L) should be reversed over 1 –2 dayInitially give normal saline to stabilize the patients hemodynamicallyThen Give 0.45% saline

2. Regular Insulin to be given intravenous

3. Subcutaneus heparin because these patients are prone to venous thrombosis.

Q. Complication in Diabetics mellitus type-II occurs around: (LQ)

A 5 years of onset

B 10 years of onset

C 15 years of onset

D 20 years of onset

Ans. B 10 years of onset In type II diabetes the chronic complication usually start after 10 years of onset of diabetes.

Chronic Complications of diabetes are:1. Vascular:a. Micro vascularb. Macro vascular

1. Microvasculari. Eye: a. Retinopathy b. Macular edemaii. Neuropathyiii. Nephropathy

2. Macrovasculari. CADii. PAD iii. CVA

3. Non vasculari. Gastrointestinalii. Genitourinaryiii. Dermatologiciv. Infectiousv. Cataractsvi. Glaucomavii. Periodontal disease

1. Vascular disease

i. Cardiovascular disease is increased in individuals with type 1 or type 2 DM.

ii. The Framingham Heart Study revealed a marked increase in PAD, CHF, CAD, MI, and sudden death (risk increases from one- to fivefold) in DM.

iii. MI is 3-5 times commoner in and is more likely to be 'silent' (without classic symptoms). Diabetes is a major risk factor for CAD.

iv. CAD is the commonest cause of death in diabetic.

v. Earliest dyslipidemia to occur is diabetes is raised Tg.

- In both the DCCT (type 1 diabetes) and the UKPDS (type 2 diabetes), cardiovascular events were not reduced immediately by intensive treatment during the trial but were reduced at follow-up 10–17 years later (this effect has been termed legacy effect or metabolic memory).

Q. The most characteristic finding in diabetic nephropathy is: (LQ)

A Diffuse glomerulosclerosis

B Nodular glomerulosclerosis

C Armani-Ebstein reaction

D Fibrin caps

1. ↑GFR is the 1st manifestation of diabetic nephropathy.

2. Then is the stage of Microalbuminuria. It is the most reliable marker of diabetic nephropathy.

-diabetes is the commonest cause of CRF

-Protein restriction is helpful in diabetic nephropathy – (H, 18th Pg- 2985)(8) Dietary advice- Protein intake = 0.8 gm/kg/day in micro Albuminuria,< 0.8 gm/ kg /day = in macro albuminuria

B) Nodular glomerulosclerosis

Pathology of Diabetic nephropathy (1) Capillary BM thickening

(2) Diffuse glomerulosclerosis (Most common). In this there is increase in mesangial matrix.

(3) Nodular glomerulosclerosis. (It is the most characteristic feature).

(4) It is accompanied by accumulation of hyalin material.

(5) If it is within capillary loop (Fibrin cap) or it is attached to Bowman capsule (Capsular drop)

(6) Armani Ebstein Reaction : Collection of glycogen clumps within the renal tubules found in diabetic nephropathy

Q. In diabetic patient fundus examination should be checked how frequently? (AIIMS May 09)

A 6 Months

B 1 year

C 2 years

D 5 years

Ans. B 1 year.

Diabetic retinopathy will be discussed in ophtho.

Q. The most common presentation of diabetic neuropathy is: (LQ)

A Amyotrophy

B Mononeuropathy

C Symmetrical sensory neuropathy

D Autonomic neuropathy

Ans. C Symmetrical sensory neuropathy

Q. Frequency of the tuning fork use for vibration sense is?

A 128

B 256

C 512

D 1024

A 128

Q.Drug used for DM gastropathy (AIIMS)

A Erythromycin

B Sulpha drug

C Tetracycline

D Ranitidine

A Erythromycin

Since erythromycin stimulates motilin receptors. And thus improvesGastric paralysis.

Skin involvement in DMa. Pigmented pretibial papulesb. Necrobiosis lipoidicac. Acanthosis nigricansd. Granuloma annularee. Lipoatrophy and lipohypertrophyf. Scleredemag. Dupuytren’s contracture.

Extra edge: Protease inhibitor can cause lipodystrophy.

Pigmented pretibial papules

MC skin manifestation of diabetes

Acanthosis nigricans

Acanthosis nigricans

DIABETIC RETINOPATHYDRUGS AND INSULIN

WILL BE DISCUSSED LATER