Diabetic Mellitus

Department of Endocrinology

Dr. Elena Ivanovna Assistant Professor, Dept. of Endocrinology, S.S.M.A.

Diabetes Mellitus Definition:is a group of common metabolic disorders characterized by Hyperglycemia due to   Decreased insulin secretion, 

Decreased glucose utilization,



Increased glucose production.

Epidemiology:

In 2000 - 171 million people all over the world were burdened with diabetes.



By 2030 - 340 million would be affected ! 

Middle east and Indian subcontinent –epidemic centre for type 2 DM.



Europe for type 1 DM.

Classification Type 1 Diabetes Mellitus.





Type 1a (Immune mediated).



1b (Idiopathic).



Type 2 DM.



Other specific types of diabetes. 

Genetic defects of Beta cell function.      

MODY 1 (Maturity Onset Disease of the Young) – HNF 4 alpha. MODY 2 – Glucokinase defect. MODY 3 – HNF 1 alpha. MODY 4 – Insulin promoter factor. MODY 5 – HNF 1 beta. MODY 6 – Neuro D1.



Genetic defects in Insulin action.



Diseases of pancreas. Pancreatitis. Neoplasia. Pancreatectomy.

  

 



Drug/Chemical induced. Glucocorticoids, Thyroid hormones, Thiazides, Beta blockers.



Infections. CMV, Congenital rubella.



Co-existent with genetic syndromes. Down’s synd, Klinefelter’s synd, Prader- Willi synd.









Endocrinopathies. Acromegaly ,Cushing's syndrome, Pheocromocytoma, Hyperthyroidism etc.

Gestational diabetes mellitus (GDM).

Insulin   

Secreted from Beta cells of Islet of Pancreas. Is an ANABOLIC hormone. Synthesized as Proinsulin. PROINSULIN

Insulin



C – peptide

Actions:

Promotes     



Glycogen synthesis. Triglyceride synthesis. Fatty acid synthesis. Protein synthesis.

Inhibits      

Gluconeogenesis. Glycogenolysis. Lipolysis. Ketogenesis. Protein degradation.



It lowers blood glucose by suppressing Hepatic glucose production and stimulating glucose uptake in Skeletal Muscle and Fat.



Measurement of C-peptide  used to assess endogenous insulin secretion.

Type 1 DM 

T cell mediated autoimmune destructive process of the beta cells of the pancreas.



Slowly progressive.



Symptoms occur when 70 – 90 % of beta cells are destroyed.



Pathological pictures  Infiltration of islets with mononuclear cells characteristic of Insulinitis.

Ethiology:Genetic 

•

HLA (Human Leucocyte Antigen) DR3 and DR4 region on short arm of chromosome 6. HLA DQA1 and DQB1 genes are also involved.

• •

Environmental 

•  

 

Viral infections  Mumps, Coxsackie B4 ,Retrovirus, Rubella, CMV, Epstein-Barr virus. Dietary habits Esp cow milk in early infancy ! Smoked and processed meats.

PATHOPHYSIOLOGICAL BASIS OF SYMPTOMS AND SIGNS OF UNCONTROLLED DM Lack of Insulin

Decreased Anabolism

fatigue

Vulvitis Balanitis

Increased Glucagon, Cortisol, GH, Catecholamines

Increased Catabolism

Glycogenolysis Gluconeogenesis lipolysis

Hyperglycemia

Wasting Loss of weight

Glycosuria Hyperketonemia

Polyuria Polydipsia

Osmotic diuresis

Tachycardia Hypotension

Salt & water depletion

Acidosis Diabetic ketoacidosis

Death ?

hyperventilation Peripheral vasodilatation Hypotension Hypothermia

Type 2 DM Pathology:

Peripheral insulin resistance.



Increased hepatic glucose production.



Impaired pancreatic beta cell function leading to relative Insulin deficiency.

Insulin resistance 

Excessive production of glucose in liver and under utilization of glucose in skeletal muscle.



Often associated with central (visceral) obesity, hypertension and dyslipidemia (increased LDL, TG, Cholesterol and decreased HDL).



Also known as Insulin Resistance Syndrome/ Metabolic Syndrome / Syndrome X / Reaven’s Syndrome.



Coexistence of central obesity ,HTN, dyslipidemia ,diabetes can lead to cardiovascular diseases.



Sedentary people without exercise are more insulin resistant than active people with the same body weight.

Etiology:Genetic 

•

• •

Is an important ethiology and varies in different ethnic groups. Susceptible loci are on Chromosome 1 q, 12 q , 20 q. Environmental 

•

   

Over eating and Inactivity. Risk is ten fold if BMI >30kg/m2. Excessive intake of sweet food. High fat food. Age 

–



Risk rises esp. in the middle ages. Pregnancy 

–



Normal insulin sensitivity is decreased through action of placental hormones in genetically predisposed females ; leads to inability of the pancreas to cope with the increased demands of insulin.

Symptoms of Diabetes:          

Polyphagia. Polyuria. Polydipsia. Nocturia. Tiredness. Recent changes in weight. Nausea / headache. Pruritis vulvae. Balanitis. Mood changes. Blurring of vision.

Investigations Urine testing

•

Glucose.

•

Mainly for screening and not for diagnosis.  Done with sensitive glucose specific urine dip sticks.  Benedict’s test.  Glycosuria is normal in pregnancy ! Ketones.

–

By Nitroprusside test. Nowadays with ketone body sensitive dip sticks.

 

Proteins.

–

Dipsticks for albumin to find out the renal disease; detects if >300mg/L of albumin is excreted through the urine.

–

Blood

–

Glucose.

–

Done in a laboratory set up. – Also with portable glucose meters; which uses capillary blood. Venous plasma values of blood glucose are the most reliable. Arterial and Capillary values will be more than the Venous values of blood glucose. –

Glycated hemoglobin (HbA1C).

–

–

Gives accurate measurement of glycaemic control over a period of weeks to months. Used for assessment of control in a patient with known Diabetes and not for diagnosis of DM. Formation of HbA1c is directly proportional to ambient glucose concentration

–

A rise of 1% HbA1c is equivalent to increase in 2 mmol/L in blood glucose.

–

Erroneously diminished in Anaemia and Pregnancy.



Glycated serum proteins (Fructosamine) can be measured which gives the glycaemic control of the preceding 2 weeks and is mainly useful in the management of diabetes in pregnancy.

–

–

Blood lipids.



• • • •

Total cholesterol. Triglycerides. LDL. HDL.

Establishing diagnosis of Diabetes.  

RBS (Random Blood Sugar) FBS (Fasting Blood Sugar)

 

> 11.1mmol/L (199mg/dl). > 7.0 mmol/L (126mg/dl).

IGT (Impaired Glucose Tolerance).  

FBS  6.1 – 7 mmol/L (110 -126 mg/dl). RBS  7.8 – 11 mmol/L (140-199 mg/dl).

OGTT (Oral Glucose Tolerance Testing). • • • • • •

unrestricted carbohydrate diet for 3 days prior to the test. Overnight fasting (at least for 8 hrs). Rest before test (30 min), no smoking, 75 grams of glucose is given mixed with a glass of water. Plasma glucose is measured before and 2 hours after. These patients have increased risks of progression to frank diabetes.

Comparative clinical features of type 1 and 2 DM Features

Type1

Type2

Typical age of onset

<40yrs

>50yrs

Duration of symptoms

Weeks

Months to years

Body weight

Normal to low

Obese

Ketonuria

Yes

No

Rapid death without treatment with insulin

Yes

No

Auto antibodies

Yes

No

Diabetic complications at diagnosis

No

25%

Family history of diabetes

Uncommon

Common

Other autoimmune diseases Common

Uncommon

Management Dietary and lifestlyle modifications. Oral antidiabetic agents. Insulin.

II. III. IV.

Therapeutic goals:Body weight to ideal level. HbA1c < 7%.

 

FBS < 6 mmol/L (108mg/dl) in type 2. 5-8 mmol/L in type 1 patients. Treatment of Hypertension and Dyslipidemia



   

B.P <140/80 mm of Hg. Total cholesterol < 5mmol/L (<190mg/dl). LDL < 3 mmol/L (<115mg/dl).

•

Life style changes:



Healthy diet. Decreased alcohol consumption. Regular exercise.

  

Quit smoking.

Plate model  Meal plan

2/5

th

Rice Pasta Bread Potatoes

Vegetables Fruits

Fish Meat Egg

1/5th

2/5th



Consumption of food with a low Glycaemic Index - as they produce a slow gradual rise in blood glucose. eg: Pasta, Brown bread, Noodles, Beans, Whole wheat products.



Daily 30 minutes of exercise walking, swimming, cycling.



Alcohol in moderation is acceptable.   



60ml of spirits/day. Half pint of beer/day. 120ml of wine/day.

Salt intake to less than 6 gm.

I.

Oral antidiabetic medications:is the mainstay of treatment for type 2 DM patients.

5.

Sulfonylureas:-

MOA  stimulate the release of insulin from the pancreatic beta cells (insulin secretalogue). Act through a sulfonlyurea receptor situated on the beta cell surface. o

To treat non obese type 2 DM patients who fails to respond to dietary measures alone.

o

Glimepiride , gliclazide , glipizide , tolbutamide , glibenclamide.

o

Can cause Hypoglycemia.

o

Strict diet control also to be maintained simultaneously.



Biguanides:-



Metformin is only available biguanide.

MOA  insulin sensitivity and peripheral glucose uptake are increased through the activation of a c- AMP regulated kinase in the muscle. Also inhibits hepatic gluconeogensis and impairs the absorption of glucose from the gut. It does NOT increase the insulin secretion. 

Given in OBESE type 2 DM.



Is synergistic with sulfonlyurea and their combination can be given.



Usually doses of 500-3000 mg/ day can be given in divide doses ( upto 3 times after food).



Contraindicated in  

Patients with impaired Renal and Liver functions. In Alcoholics because of the risk of developing Lactic Acidosis.



Alpha – Glucosidase inhibitors:-



They delay the carbohydrate absorption in the gut by selectively inhibiting disaccharidases.



Acarbose and Miglitol



Lower the post prandial blood glucose , and is usually combined with a sulfonylurea.



Side effects  flatulence, abdominal bloating , diarrhea.



Thiazolidinediones:-

MOA  bind and activate peroxisome proliferator activated receptor alpha , a nuclear receptor present mainly in adipose tissue which regulates the metabolism and enhances the actions of endogenous insulin. 

Rosiglitazone and Pioglitazones.



Combined with insulin or sulfonlyureas.



Most effective in patients with severe insulin resistance (in central obesity). They redistribute the fat to subcutaneous areas. However the body fat and weight is increased.



Side effect  sodium and fluid retention.



Hence avoided in cardiac failure.



Meglitinides and Amino acid derivatives:-



Are also called prandial glucose regulators.



Repaglinide directly stimulates endogenous insulin secretion and is taken immediately after the food.



Nateglinide also has similar action.



Incretin Mimetics:-



secretion of insulin in response to a rise in blood glucose is greater when glucose is given by mouth rather than by i.v. infusion. It is caused by secretion of gut hormones or Incretins. GLP – 1 (Glucagon Like Peptide) is an incretin hormone which stimulates insulin secretion in a glucose dependent manner, thus hypoglycemia is rare. It also suppresses glucagon secretion , delays gastric emptying, reduces appetite and encourages weight loss.



 



Is given as an injection. As GLP – 1 is rapidly degraded by dipeptidyl peptidase IV, inhibitors of this enzyme also has to be given along. Long acting GLP – 1 analogues  Liraglutide , Exenatide.



Insulin:-

•

Before from extraction and purification from the pancreas of cows and pigs.

•

Nowadays made by recombinant DNA technology.

Insulin delivery  •

Injected subcutaneously into the anterior abdominal wall , upper arms , outer thighs and buttocks.

•

Administered using a disposable plastic syringe with a fine needle.

•

Also available as Pen injectors with cartridges which are more convenient.

•

Also available as “Open – Loop ” systems ; which are battery empowered providing continuous subcutaneous or intravenous infusion of insulin.

•

Intra nasal insulin has been recently approved by FDA and will be soon available in the market!

•

Technique  needle to be at right angle to the skin and injection is given subcutaneously and not intramuscular.

Insulin

Types of Insulin and its duration of action (in hours) Onset Peak

Duration

Rapid acting (insulin Lispro, Aspart, Glulisine).

<0.5

0.5 – 2.5

3 – 4.5

Short acting (Soluble / Regular insulin)

0.5 – 1

1–4

4–8

Intermediate acting (Isophane(NPH), Lente)

1–3

3–8

7 – 14

Long acting ( Glargine, Detemir)

1–2

None

18 – 24

Insulin regimens:

Choice of regimen depends on desired degree of glycemic control, patient’s lifestyle, and his/ her ability to adjust the insulin dose.



Twice daily regimen of a short acting and intermediate acting insulin given in combination with breakfast and dinner is the simplest regimen followed.



2/3rd of the total dose is given in the morning and 1/3rd in the evening.



Ratio of short : intermediate insulin is 1 : 2.



Doses are adjusted according to blood glucose measurements.



Pre-mixed formulations are available.



Available in variable ratios (short : intermediate) of 30:70 , 50:50 etc.



Multiple injection regimens.



Short acting insulin taken before each meal and intermediate insulin being used at bed time (Basal –Bolus regimen).



Snacks have to be taken in such an regimen to avoid hypoglycemia.

Side effects of insulin therapy:

Hypoglycemia.



Weight gain.



Peripheral edema (as insulin causes water and salt retention in short term).



Insulin antibodies (while using animal insulins).



Local allergy.



Lipodystrophy at injection sites.

Gestational Diabetes Mellitus Definition:Diabetes with first onset or recognition during pregnancy. Incidence:2 – 4 % of all pregnancies. Risk factors:     

Age > 25yrs. Obesity. First degree relatives of type 2 DM. Ethnicity. Previous GDM. Previous macrosomic baby (>4kg).

Screening and Diagnosis :

Any pregnant woman with one or more risk factors to be evaluated at the beginning of third trimester (at 28 weeks).



50 gram glucose challenge test , measuring blood glucose one hour later.



If abnormal ( > 7.8 mmol/L), then 75 gram OGTT to be performed.



If any two out of three values are met or exceeded the diagnosis of G.D.M is made.  F.B.S  > 5.3 mmol/L.  1 hour value  >10.6 mmol/L.  2 hour value  > 8.9 mmol/L.

Effects on Fetus 

Maternal hyperglycemia induces hyperinsulinemia in fetus.



Results in Macrosomia (insulin acts as a growth factor).



Prone to respiratory distress , neonatal hypoglycemia , hypocalcemia , hyeprbilirubinemia , polycythemia , IUGR.



Prone to congenital deformities if diabetes pre dates pregnancy.

Maternal effects:

Increased risk of developing type 2 DM.



Progression of Diabetic Nephropathy and Retinopathy.

Management:9.

Preconception care to normalize Hba1c level.

11.

Tight glycemic control.

13.

Oral hypoglycemics are contra indicated.

15.

Insulin to control diabetes if diet control is inadequate.

17.

Careful fetal monitoring through out pregnancy.

Diabetic Ketoacidosis Pathophysiology:-





Insulin deficiency combined with increased counter regulatory hormones such as Glucagon ,GH , Cortisol , Catecholamines.



Clinically involves two factors  

Lack of insulin(non compliance,inadequate dose,initial presentation of DM).



Precipitant (surgery, stress, infection, emotional stress).



Unrestricted hepatic glucose production  hyperglycemia.



Lipolysis resulting in free fatty acids  ketoacids  acidosis.



Osmotic diuresis causing dehydration and electrolyte disturbances.



Clinical features:

Typical patient Type 1 DM.



Preceded by polyuria and polydipsia.



High serum osmolality (>330 mosm).



Dehydrated and ketoacidotic. 

Anorexia , nausea, vomiting, fatigue.



Abdominal pain (esp in children).



Kussmaul’s respirations (rapid deep breathing).



Investigations and laboratory findings:

Plasma glucose, BUN, serum electrolytes, creatinine, ketones.



Urine glucose and ketones.



Hyperglycemia and ketonemia.  



Blood glucose elevated. Ketones in range of 15 mmol/L.

Wide anion gap metabolic acidosis (pH <7.3 and/or HCO3 <15) plus possible secondary respiratory alkalosis due to Kussmaul’s respirations; can also have metabolic alkalosis from vomiting and dehydration.

Anion gap = [Na+ - (Cl- + HCO3-)] meq/L

Treatment:

Rapid diagnosis and medical supervision are essential.



Monitor degree of ketoacidosis with anion gap and not blood glucose or ketone level.



Rehydration 

To maintain adequate cardiac output and renal perfusion.



Usually 6 liters have to be given.  3 L of extracellular fluid loss to be replenished with Normal Saline.  3 L of intracellular loss with Normal Dextrose.



Normal saline i.v.  1 L over 30 min.  1L over 1 hour.  1 L over 2 hours.  1 L over next 2 -4 hrs.



When blood glucose <15mmol/L (270mg/dl) switch to 5% dextrose, 1 litre over 8 hours.





Insulin 

Initial bolus dose of 5-10U ( or 0.1U/Kg body weight) I.V. in adults.



Followed by continuous infusion at 5-10 U (0.1 U/Kg) per hour.



When bd. Glucose falls < 15 mmol/L insulin reduced to 3 units/hr (0.05 U/Kg/hr).



When <10 mmol/L  2units/hr.



Aim for 3-6 mmol fall in blood glucose per hour.

Potassium 

Avoid hypokalemia.



K+ is lost from cells due to insulin deficiency and general catabolic state.



Blood levels will not reflect the total body losses which might be about 400-500 mEq.



K+ falls during treatment due to rehydration and insulin (drives K+ into cells).



Normal or low initial K+ indicates severe deficiency and requires cardiac monitoring.





If < 3.5 mmol/L, give 40 mmol in 1 litre fluid.avoid infusion rate of >20 mmol/hr.



If 3.5 – 5 mmol/L , give 20 mmol of pottasium.



If >5 , dont give any.

Bicarbonate 

Given only in life threatnening and /or shock only.



Corection always done partially.



Treatment of the precipitating causes and patient education to prevent further DKA episodes.



In case of Cerebral Edema ,I.V. Mannitol is given.

Prognosis: 

2-3 % mortality in developed countries. Morbidity and mortality due to  Sepsis.  Pulmonary and CVS complications.  Thromboembolic events.  Cerebral edema.

Hyperosmolar Nonketotic Hyperglycaemia Syndrome Etiology:

Usually complication of type 2 DM.



Profound dehydration resulting from hyperglycemia.



Precipitating eventsstroke , MI , Trauma , drugs (glucocorticoids, immunosuppressants , diuretics), medical procedures (dialysis), burns.

Clinical Features:

Extreme hyperglycemia, hyperosmolality, dehydration and CNS signs.

Lab findings:

High urine glucose and negative or low ketones.



Blood glucose is often > 55 mmol/L ; but is not a good indicator of the severity.



High serum osmolality.



Electrolytes may show false hyponatremia ( because fall of 3 mEq/L of Na+ for every 10mmol/L increase of blood glucose).



Same lab findings can be due to some other acute conditions such as  sepsis, renal failure, Lactic Acidosis.

Treatment:Insulin

• 

Usually given I.V. at the rate of 3 units/ hour.

Intravenous Fluids

•

PLASMA OSMOLALITY = 2[Na+] + 2[K+] + [Glucose] + [Urea] in mmol/L

•



Normal value is 280 – 300 mmol/Kg.



Consciousness is depressed if >340 mmol/Kg.



Patient is give 0.45% Normal Saline until osmolality reaches normal.



Then it is substituted with Isotonic (0.9%) Saline.



Rate of replacement regulated with Central Venous Pressure (CVP) and plasma Sodium concentration. Thromboembolic complications are common so prophylactic s.c. low molecular weight Heparin is given.

Lactic Acidosis 

Mainly due to therapy with Metformin in type 2 DM patients.



Patient will be very ill and over-breathing (but without acetone smell as in case of other hyperglycemic coma’s).



Plasma HCO3- and pH  markedly reduced; (H+ > 63mmol/L , pH < 7.2).



Anion gap  increased.



Diagnosis confirmed by high ( >5mmol/L) conc. of Lactic acid in the blood.



Treatment   



I.V. sodium bicarbonate until arterial pH raises above 7.2 ; Insulin and Glucose.

Associated with high mortality rate of about 50% in spite of best treatment !

Hypoglycemia Definition:as the plasma glucose level < 2.5 to 2.8 mmol/L (<45 to 50 mg/dl). To diagnose hypoglycaemia criteria is Whipple’s Triad. 1. 2. 3.

Symptoms consistent with hypoglycaemia. Low plasma glucose concentration at the time of symptoms. Relief of hypoglycemic symptoms after the Treatment.

Usually seen in patients treated with Insulin and Sulphonylureas.

Clinical features:Adrenergic symptoms 

 

Palpitations, Sweating, Anxiety, Hunger, Tremors, Tachycardia. Neuroglycopenic symptoms 

 

Headache, Mental dullness, Fatigue, Confusion, Amnesia, Seizures, Coma.

Types:Postprandial (Reactive) Hypoglycaemia.

•

   

Occurs after 1.5 to 6 hours after a meal and recovers spontaneously. Mainly manifested as Adrenergic symptoms. Post GI surgeries (Gastrectomy, Pyloroplasty, Vagotomy). Treatment is with small feeds and weight loss.

Fasting Hypoglycaemia.

•

•





Due to imbalance between production of glucose by liver and utilization by peripheral tissues. Etiology • Impaired production of glucose. • Hormone deficiencies (Hypopituitarism, Adrenal insufficiency). • Liver diseases (cirrhosis, uremia). • Drugs (alcohol,Salicylates, Propanolol). due to overutilization of glucose. • Hyperinsulinism (Insulinoma, Sulfonylurea, exogenous Insulin, Sepsis). • Extra pancreatic tumours. • Treatment is by treating the underlying cause.

Treatment:If conscious. Carbohydrates (a glass of fruit juice , aerated soft drinks, chocolate, glucose powder, Jam, honey etc ). 

Unconscious/ not able to swallow. 

I.V. glucose 30 – 50ml of 20–50 % dextrose followed by normal saline flush.



(or) Glucagon  1 mg i.m.



Dose of glucose to be given in children is 0.2 g/ Kg i.v.



Once patient gains consciousness glucose can be given orally.

Complications of DM. 

Majority of complications are due to :

Macroangiopathies. Most common cause of death in type 2 DM.  Accelerated atherosclerosis leading to  Coronary artery disease.  Stroke.  Peripheral vascular disease.



Microangiopathies. Major chronic complication of type 1 & 2 DM.  Mainly Retinopathy, Nephropathy, Neuropathy.  Can involve other organs like heart , skin etc.



Aggravating factors like :   

Poor glycemic control. Inadequate control of hypertension and cholesterol. Smoking High fat diet.

Diabetic Retinopathy. Epidemiology:Present in 50% of patients after 10 yrs of DM.



Types:Non- Proliferative (Background) Retinopathy 

  

Venous dilatations, peripheral microaneurysms, blot hemorrhages, exudates. No threat to the vision.

Maculopathy 

  

Exudation, hemorrhage, ischemia of the macula. Sight threatening.

Pre- Proliferative Retinopathy 

  

Venous loops, microaneurysms, small blot hmgs / large retinal hmgs, intraretinal microvascular abnormalities, multiple cotton wool spots, macular edema. Sight threatening.

Proliferative Retinopathy 

  

Pre retinal hmgs, neovascularisation, fibrosis, exudative maculopathy. Sight threatening.

Pathogenesis:

Hyperglycemia increases retinal blood flow and metabolism and has direct effects on retinal endothelial cells and pericyte loss, leading to impairment of vascular auto regulation.



Leads to chronic retinal hypoxia, new vessel formation, and increased vascular permeability.

Clinical features :       

Microaneurysms. Hemorrhages  usually blot hmgs (in deeper retinal layers). Exudates. Cotton wool spots. Intraretinal microvascular abnormalities. Neovascularisation. Venous changes. Rubeosis iridis  formation of new vessels on the anterior surface of iris and can lead to 2 0 glaucoma.

Prevention and management :5.

Tight glycaemic control.

7.

Blood pressure control.

9.

Screening for retinopathy, in all patients with DM.

11.

Photocoagulation. 

Argon laser photocoagulation is most commonly used



Pan retinal photocoagulation.



To destroy areas of retinal ischemia, to seal leaking microaneurysms and reduce macular edema, to gliose new vessels directly on the retinal surface.



Vitrectomy  in cases of advanced diabetic eye diseases.



Frequent follow up visits to an Ophthalmologist.

Diabetic Nephropathy. Epidemiology:

Most common cause of ESRF (End Stage Renal Failure).



40 % of patients with type 1 and 4 – 20 % with type 2 has diabetic nephropathy.

Pathology:

Thickening of the glomerular basement membrane.



Accumulation of matrix material in the measangium.



Nodular deposits.



Glomerulosclerosis.

Presentation :Initially  increased G.F.R (Glomerular Filtration Rate) upto 140 % , enlarged kidneys, microalbuminuria.





Over 15 yrs progress to cause hypertension , persistent proteinuria (microalbuminuria), Nephrotic syndrome, renal failure.

Management :11.

Tight glycemic control.

13.

Tight blood pressure control . 

A.C.E inhibitors.



Ca2+ blockers.

15.

Limiting or avoiding use of Nephrotoxic drugs and Dyes.

17.

Renal transplant alone or in combination with pancreatic transplant.

Diabetic neuropathy. Epidemiology:

Common in type 1 and 2 DM.

Pathophysiology:

Metabolic defects due to either increased Sorbitol or decreased Myoinositol.



Axonal degeneration of both myelinated and unmyelinated fibres.



Thickening of Schwann cell basal lamina.



Patchy segmental demyelination.



Thickening of basement membrane and micro thrombi in intraneural capillaries.

Classification of Diabetic Neuropathy. Somatic. Polyneuropathy. Symmetrical,

mainly sensory and distal.

Asymmetrical,

mainly motor and proximal.

Mononeuropathy.

Visceral (autonomic). CVS. GIT. Genitourinary. Vasomotor. Pupillary.

Clinical features:Symmetrical sensory polyneuropathy.





Diminished vibration perception in the distal parts of the body (Glove and Stocking type).



Sensory abnormalities  pain, burning sensation etc.



Loss of tendon reflexes in the lower limbs.



Paresthesia of the feet.



Wasting of interosseous muscles leading to clawed toe.

Asymmetrical sensory polyneuropathy.

4. 

Severe and progressive weakness and wasting of proximal muscles of the lower limbs.



Severe pain.



Sometimes marked loss of weight.

Mononeuropathies.

1.



Either sensory or motor function affected within a single nerve.



Commonly affected  3rd , 6th cranial nerves resulting in Diplopia.



Carpal tunnel syndrome due to compression of median nerve.



Sometimes foot drop due to lateral popliteal N. compression.

Autonomic neuropathy.

3.     

    

Postural hypotension. Resting tachycardia. Dysphagia. Diarrhoea / constipation. Difficulty in micturition / urinary incontinence / recurrent infection due to atonic bladder. Nocturnal sweats. Dependent edema. Cold feet. Decreased pupil size. Erectile dysfunction.

Management:

Strict glycemic control.



For pain     

12.

Erythromycin , metoclopromide for gastric paresis.

14.

Loepramide for diarrhea.

16.

Self intermittent catheterization for Atonic bladder.

18.

For erectile dysfunction  phosphodiesterase type 5 inhibitors (Sildenafil , Vardenafil).

Tricyclic anti - depressants (Amitryptiline, Imipramine). Capsaicin. Anti – convulsants (Gabapentin, Carbamazepine, Phenytoin, Pregabalin). Opiates (Tramadol , Oxycodone). Anti – oxidants (alpha lipoic acid).

psychological counselling and implanted penile prosthesis.

The End…. Dr. Elena Ivanovna, Ivanovna Assistant Professor, Endocrinology, S.S.M.A.