Diabetes Mellitus. A clinical case where there is relative or total absence of insulin, which...

Diabetes Mellitus

Diabetes Mellitus

Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus

A clinical case where there is relative or total absence of insulin, which reduces

glucose uptake and utilization by insulin-sensitive tissues and leads to serious

long term complications.

A clinical case where there is relative or total absence of insulin, which reduces

glucose uptake and utilization by insulin-sensitive tissues and leads to serious

long term complications.

Insulin release

Glucose is most potent stimulus for insulin release from cells. There is continuous basal secretions with peaks at feeding times.

Insulin release

Glucose is most potent stimulus for insulin release from cells. There is continuous basal secretions with peaks at feeding times.

What is diabetes ?What is diabetes ?

Types of Diabetes MellitusTypes of Diabetes Mellitus

Diabetes MellitusDiabetes Mellitus

Pathogenesis:Autoimmune disease or viral infection (e.g. mumps) or enviromental toxins β cell destruction plasma insulin level is low or even immeasurable

Sometimes type I appears late in adulthood latent autoimmune diabetes in adult (LADA) islet cell function and insulin antibodies tests should be performed in non-obese adult to exclude type 2 diabetes

Pathogenesis:Autoimmune disease or viral infection (e.g. mumps) or enviromental toxins β cell destruction plasma insulin level is low or even immeasurable

Sometimes type I appears late in adulthood latent autoimmune diabetes in adult (LADA) islet cell function and insulin antibodies tests should be performed in non-obese adult to exclude type 2 diabetes

Type I (IDDM) Insulin dependant DM

Age onset: juvenile (young age)

Diabetes MellitusDiabetes Mellitus

Type II (NIDDM) Non-insulin dependant DM

Age onset: maturity onset (after 40 years)

Pathogenesis:Insulin resistance ( peripheral glucose utilization hyperglycemia insulin secretion then after time β cell exhaustion defective insulin secretion

Type 2 diabetic patients are divided into:-obese individuals (insulin resistance predominates)-non-obese individuals (defective insulin secretion predominates)

Pathogenesis:Insulin resistance ( peripheral glucose utilization hyperglycemia insulin secretion then after time β cell exhaustion defective insulin secretion

Type 2 diabetic patients are divided into:-obese individuals (insulin resistance predominates)-non-obese individuals (defective insulin secretion predominates)

Types of Diabetes MellitusTypes of Diabetes Mellitus


Other types of diabetes

- Gestational diabetes- 2ry diabetes (acromegaly, cushing, cystic fibrosis-related diabetes, drug related e.g. thiazide, phenytoin)

Other types of diabetes

- Gestational diabetes- 2ry diabetes (acromegaly, cushing, cystic fibrosis-related diabetes, drug related e.g. thiazide, phenytoin)

Insulin deficiency or resistance

Glucose uptake Glucose uptake

Hyperglycemia

Glucosuria

Osmotic diuresis

Dehydration

Polydipsia

Electrolyte imbalance

Hyperglycemia

Glucosuria

Osmotic diuresis

Dehydration

Polydipsia

Electrolyte imbalance

plasma a.a. & -ve nitrogen

balance

plasma a.a. & -ve nitrogen

balance

Protein catabolism Protein catabolism lipolysislipolysis

plasma FFA

ketogenesis

ketonuria

plasma FFA

ketogenesis

ketonuria

Dehydration & acidosisDehydration & acidosis

Coma & deathComa & death


Diabetic Diabetic ketoacidosis (DKA)ketoacidosis (DKA)Insulin Insulin

DeficiencyDeficiencyIncreased Increased lipolysislipolysisFFA + GlycerolFFA + Glycerol

IncreaseIncreased Acetyl d Acetyl

CoACoAAcetoacetic Acetoacetic

acidacid-hydroxybutyric -hydroxybutyric acidacid

AcetoneAcetone

DKADKA

ReductioReductio

nn

Decarboxylatio

Decarboxylationn

The body responds to ketoacidosis by

hyperventilatin, why?Due to acidosis respiratory center to get rid of CO2 in blood stream which is an acidic moiety blood pH compensating for the case of metabolic acidosis.


Symptoms Symptoms

Long Term ComplicationsLong Term Complications

Microvascular complication

Microvascular complication

Macrovascular complication

Macrovascular complication

Retina( diabetic retinopathy)

blindness

kidney( diabetic nephropathy)

Renal failure

-Numbness-Reduced sensation in the lower extremities-Erectile dysfunction (also from reduced blood flow to the penis)

nerves( diabetic neuropathy)

Microvascular complication Microvascular complication

thickening of capillary basement membrane thickening of capillary basement membrane

Macrovascular complication Macrovascular complication

•Accelerated atherosclerosis ( LDL).•Narrowing of artery lumen and reduce blood flow.•Plaque rupture ( risk of thrombosis).

•Accelerated atherosclerosis ( LDL).•Narrowing of artery lumen and reduce blood flow.•Plaque rupture ( risk of thrombosis).

Coronary arteries

coronary heart diseases heart attack, myocardial

infarction),

peripheral arteries

Ischemia and thrombosis

cerebral arteries

stroke

Diabetic feet careDiabetic feet careComplications of foot injury

Neuropathy (patients not aware of injuries to the feet). Poor blood circulation (micro- and macrovascular disease) slow wound healing. body immune system favors infection and anaerobic bacterial growth. The spread of gangrenous infection into blood stream can be life-threatening. Amputation of the limb may be done to prevent this possibility.


ComplicationsComplications

Diabetic Diabetic UlcerUlcer

Diabetic footDiabetic foot

Gum ulcersGum ulcers CataractCataract


DiagnosisDiagnosis

Laboratory test Specimen Normal values

Blood glucose (fasting) plasmaplasma 70-110 mg/dl70-110 mg/dl

Blood glucose (postprandial 2hrs) plasmaplasma 110-180 mg/dl110-180 mg/dl

Urine analysis for glucose & acetone Urine Urine ------------

Glycosylated haemoglobin(HbA1c)

Whole blood Whole blood 5-8%5-8%

Plasma C-peptide Whole blood Whole blood 0.5 - 2.0 ng/mL0.5 - 2.0 ng/mL

A.A. Physical ExaminationPhysical Examination

B.B. Laboratory tests Laboratory tests


DiagnosisDiagnosisGlycosylated haemoglobin (HbA1c)

• Non enzymatic binding of glucose to Hb ( diabetes due to blood glucose level) • It indicates diabetic control over the past three mouths (life span of RBCs).


DiagnosisDiagnosisC-peptide Measurement

Advantages1.1. More sensitive than HbMore sensitive than HbA1c.A1c.

2. Higher t2. Higher t½½ than insulin, so than insulin, so

more reliablemore reliable

3. Higher urinary concentration 3. Higher urinary concentration than insulin.than insulin.

Uses1.1. Monitor Monitor -cell function in NIDDM-cell function in NIDDM

2.2. Differentiate between IDDM & Differentiate between IDDM & NIDDMNIDDM

• This test indicates β cell function by determining level of endogenous insulin secretion equivalent to C- peptide level.• C-peptide level is low in type I diabetes and high but not always in type II diabetes or insulin resistance.


DiagnosisDiagnosisPrediabetic patients impaired glucose tolerance (IGT) glucose levels between normal and diabetic Weight loss and exercise may help these people and sometimes the use of insulin sensitizers such as metformin is necessary in early diabetic patient of type II

Prediabetic patients impaired glucose tolerance (IGT) glucose levels between normal and diabetic Weight loss and exercise may help these people and sometimes the use of insulin sensitizers such as metformin is necessary in early diabetic patient of type II


Usually happens due to mismatching between insulin dose and diet or exerciseClinicallyCold clammy sweat.Coma.Management:100 cc glucose 50% slowly and monitor blood sugar or intramuscular glucagon injection. Glucagon causes the release of glucose from the liver (by promoting glycogenolysis and gluconeogenesis).

Hypoglycemic ComaHypoglycemic Coma


Summary of some insulin preparationsSummary of some insulin preparations

Ultra-short-actingUltra-short-actingInsulin lispro (Humalog)Insulin lispro (Humalog)

Short acting insulinShort acting insulinRegular (Crystalline Zn)Regular (Crystalline Zn)

Intermediate actingIntermediate actingNeutral protamine Hagedorn (NPH) insulinNeutral protamine Hagedorn (NPH) insulin

Premixed (biphasic)Premixed (biphasic)%NPH, % regular%NPH, % regularHumulin 70/30Humulin 70/30

Long acting insulinLong acting insulinInsulin glargineInsulin glargineInsulin detemirInsulin detemir

TreatmentTreatment

Insulin Insulin regimensregimens

Basal-bolus regimen

Twice-daily regimen


SULPHONYLUREA COMPOUNDSSULPHONYLUREA COMPOUNDS (Long acting secretagogues)(Long acting secretagogues)11stst generation: generation: Tolbutamide, chlorpropamide.Tolbutamide, chlorpropamide.

22ndnd generation: generation: Glibenclamide (DaonilGlibenclamide (Daonil®®)) Gliclazide (DiamicronGliclazide (Diamicron®®)) Glimepiride (AmarylGlimepiride (Amaryl®®))

Oral Oral HypoglycemicsHypoglycemics

SULPHONYLUREA COMPOUNDSSULPHONYLUREA COMPOUNDS (Long acting secretagogues)(Long acting secretagogues)N.B. glipizide is the only SU that can be N.B. glipizide is the only SU that can be used in poor renal function.used in poor renal function.Adverse effects:Adverse effects:Common: Hypoglycemia, weight gain.Common: Hypoglycemia, weight gain.


BIGUANIDESBIGUANIDES Metformin (GlucophageMetformin (Glucophage®®))

MOA: reduces hepatic gluconeogenesis, reduces intestinal MOA: reduces hepatic gluconeogenesis, reduces intestinal absorption of glucose and has favourable effect on insulin absorption of glucose and has favourable effect on insulin senstivity. In addition to anorexic effect.senstivity. In addition to anorexic effect.S.Es. S.Es. Common: N/V, diarrhea and epigastric pain.Common: N/V, diarrhea and epigastric pain.Less common: lactic Less common: lactic acidosis acidosis metformin should not be recommended in patient with poor renal function so as to avoid lactic acidosis



MeglitinidesMeglitinides Repaglinide and nateglinideRepaglinide and nateglinide

MOA: Similar to that of sulphonylureas in increasing insulin MOA: Similar to that of sulphonylureas in increasing insulin secretion from the pancreas but with a very rapid onset and secretion from the pancreas but with a very rapid onset and shorter duration of activity.shorter duration of activity.S.Es. S.Es. Common: hypoglycemia and weight gainCommon: hypoglycemia and weight gain



Thiazoldindiones (TZDs or glitazones)Thiazoldindiones (TZDs or glitazones) Pioglitazone and RosiglitazonePioglitazone and Rosiglitazone

MOA: PPARMOA: PPARagonist agonist →↑expression of genes →↑expression of genes responsible for glucose metabolism, resulting in responsible for glucose metabolism, resulting in improved insulin sensitivity.improved insulin sensitivity.In Semptember 2010, FDA initiated restriction access to In Semptember 2010, FDA initiated restriction access to Rosiglitazone concerned with cardiovascular safety.Rosiglitazone concerned with cardiovascular safety.Pioglitazone Pioglitazone may cause may cause fluid retention (resistant edema)fluid retention (resistant edema)



Dipeptidyl peptidase-4 (DPP-4) inhibitorsDipeptidyl peptidase-4 (DPP-4) inhibitors Sitagliptin & SaxagliptinSitagliptin & Saxagliptin

MOA: inhibits the breakdown of glucagon-like peptide-1 MOA: inhibits the breakdown of glucagon-like peptide-1 (GLP-1) secreted during meals, which in turn increases (GLP-1) secreted during meals, which in turn increases pancreatic insulin secretion, limits glucagon secretion, slows pancreatic insulin secretion, limits glucagon secretion, slows gastric emptying, and promotes satietygastric emptying, and promotes satiety..



-GLUCOSIDASE INHIBITORS-GLUCOSIDASE INHIBITORS Miglitol (GlysetMiglitol (Glyset®®) - Acarbose (Glucobay) - Acarbose (Glucobay®®))Decreases intestinal absorption of glucoseDecreases intestinal absorption of glucose



Diabetic ketoacidosisDiabetic ketoacidosis Results in significant hyperglycemia, dehydration Results in significant hyperglycemia, dehydration and ketoacidosis.and ketoacidosis.Signs/symptoms: polyuria, polydipsia, vomiting, Signs/symptoms: polyuria, polydipsia, vomiting, dehydration, altered mental status, coma.dehydration, altered mental status, coma.Treatment:Treatment:1.1.Fluid replacement: saline (0.9%).Fluid replacement: saline (0.9%).2.2.Insulin I.V. (Bolus or infusion).Insulin I.V. (Bolus or infusion).3.3.KCL (IV) in case of hypokalemia.KCL (IV) in case of hypokalemia.4.4.IV bicarbonate if serum pH less than 6.9.IV bicarbonate if serum pH less than 6.9.

Treatment of DMTreatment of DMcomplicationscomplications


NephropathyNephropathyACE inhibitors and ARBs are often used regardless of ACE inhibitors and ARBs are often used regardless of whether the patient has hypertension or not.whether the patient has hypertension or not.RetinopathyRetinopathyNo specific pharmacotherapy recommended except to No specific pharmacotherapy recommended except to adequate glucose control and BP.adequate glucose control and BP.



DM NeuropathiesDM NeuropathiesA-Neuropathic painA-Neuropathic pain1.1.TCAs ( amitriptyline, desipramine)TCAs ( amitriptyline, desipramine)2.2.Anticonvulsant (gabapentin, lamotrigine, pregabalin)Anticonvulsant (gabapentin, lamotrigine, pregabalin)Pregabalin is recommended in the treatment of DM Pregabalin is recommended in the treatment of DM neuropathyneuropathy3. SSRIs especially duloxetine or SNRIs .3. SSRIs especially duloxetine or SNRIs .B-GastroparesisB-GastroparesisAutonomic neuropathy causes considerable N/V after Autonomic neuropathy causes considerable N/V after meals because of delayed gastric emptying.meals because of delayed gastric emptying.ttt: prokinetics drugs such as metoclopramide, ttt: prokinetics drugs such as metoclopramide, domepridone or erythromycin.domepridone or erythromycin.



Cardiovascular diseasesCardiovascular diseasesA-BP managementA-BP managementACE inhibitors or ARBsACE inhibitors or ARBsB-Lipid managementB-Lipid managementStaitnsStaitnsAntiplatelet as Aspirin or Clopidogrel may be added Antiplatelet as Aspirin or Clopidogrel may be added with existing cardiovascular diseases to prevent with existing cardiovascular diseases to prevent ischemic heart diseases.ischemic heart diseases.



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