Diabetes Mellitus

JI Barrozo, Caoile, Carrascal

Diabetes Mellitus
Group of metabolic disorders

Hyperglycemia

Genes and Environmental Factors

Diabetes Mellitus: Factors for its development

1 2 3

Reduced insulin secretion Decreased glucose utilization

Increased glucose production

Diabetes Mellitus: Secondary Pathologies

End-stage renal disease (ESRD) Non-traumatic lower extremity amputations

Adult blindness
Increased predisposition to cardiovascular diseases

Insulin Biosynthesis
Produced in the beta cells of the pancreatic islets

Initially a single-chain 86-amino-acid precursor polypeptidePREPROINSULIN

Proteolytic processing removes the aminoterminal signal peptide PROINSULIN.

Cleavage of an internal 31-residue fragment from proinsulin C peptide and the A (21 amino acids) and B (30 amino acids) chains of INSULIN, connected by disulfide bonds.

Insulin Secretion

Glucose levels >3.9 mmol/L (70 mg/dL) stimulate insulin synthesis

Insulin Action

DM: General Classification

Type I
Complete

Type II Others
Insulin resistance Impaired insulin secretion MODY

Gestational DM Pancreatic Exocrine Disease

Near-total insulin deficiency

Increased glucose production

DM Type I

Genetic, Environmental, Immunologic factors

Destruction of the pancreatic beta cells

Insulin deficiency

DM Type I

Features of diabetes do not become evident until a majority of beta cells are destroyed (7080%).

DM Type II

Insulin

resistance and abnormal insulin secretion Insulin resistance precedes an insulin secretory defect but that diabetes develops only when insulin secretion becomes inadequate.

DM Type II

Diabetes mellitus
Diabetes mellitus

Normal Glucose Tolerance

An

FPG <5.6 mmol/L (100 mg/dL), Plasma glucose <140 mg/dL (11.1 mmol/L) following an oral glucose challenge, A1C <5.6% are considered to define normal glucose tolerance

Criteria for Diagnosis

Symptoms of diabetes plus random blood glucose concentration 11.1 mmol/L (200 mg/dL) or
Random is defined as without regard to time since the last meal

Fasting plasma glucose 7.0 mmol/L (126 mg/dL)bor

Fasting is defined as no caloric intake for at least 8 h

A1C > 6.5%cor

test should be performed in laboratory certified according to A1C standards of the Diabetes Control and Complications Trial

Two-hour plasma glucose 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance testd
glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water

Risk Factors for DM Type II

Family

history of diabetes (i.e., parent or sibling with type 2 diabetes) Obesity (BMI 25 kg/m2) Physical inactivity Race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander) Previously identified with IFG, IGT, or an A1C of 5.76.4%

Risk Factors for DM Type II

History

of GDM or delivery of baby >4 kg (9 lb) Hypertension (blood pressure 140/90 mmHg) HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L) Polycystic ovary syndrome or acanthosis nigricans History of cardiovascular disease

Acute Complications of DM

Diabetic ketoacidosis (DKA) and Hyperglycemic Hyperosmolar State (HHS)

Acute Complications of DM

Diabetic ketoacidosis (DKA)

Characterized by hyperglycemia, ketosis, and metabolic acidosis Ketones 5 meq/L Increased blood glucose pH < 7.3 (~6.8-7.3) Serum bicarbonate 10 mEq/L Manifestations

Tachycardia Dehydration/hypotension Tachypnea Abdominal tenderness Changes in sensorium

Acute Complications of DM

Hyperglycemic Hyperosmolar State (HHS)

an elderly individual with type 2 DM, with a several week history of polyuria, weight loss, and diminished oral intake that culminates in mental confusion, lethargy, or coma

Manifestations

Profound Dehydration and hyperosmolality and reveals hypotension, tachycardia, and altered mental status Absent are symptoms of nausea, vomiting, and abdominal pain and the Kussmaul respirations characteristic of DKA

Diabetic Nephropathy

Leading

cause of ESRD in the US Leading cause of DM-related morbidity and mortality Microalbuminuria and macroalbuminuria associated with increased CV disease diabetic retinopathy

Pathogenesis
1
Hyperglycemia

Activation of soluble factors VEGF, TGF-beta, AGEs

Hemodynamic alterations in the renal microcirculation

Structural changes in the glomerulus Increased extracellular matrix, BM thickening, mesangial expansion, fibrosis

Time Course of Development

Radiocontrast-induced nephrotoxicity
Risk

factors

Preexisting nephropathy Volume depletion

Treatment
Optimal

therapy: prevention by control of glycemia

Screening for microalbuminuria

 Interventions

effective in slowing progression from microalbuminuria to macroalbuminuria include

(1) normalization of glycemia (2) strict blood pressure control (3) administration of ACE inhibitors or ARBs.

Dyslipidemia should also be treated.

 Improved

glycemic control reduces the rate at which microalbuminuria appears and progresses in type 1 and type 2 DM.

 During

the later phase of declining renal function, insulin requirements may fall as the kidney is a site of insulin degradation.

 Many

individuals with type 1 or type 2 DM develop hypertension. pressure should be maintained at <130/80 mmHg in diabetic individuals.

Blood

Drugs

ACE inhibitors ARBS If use of either ACE inhibitors or ARBs is not possible or the blood pressure is not controlled
calcium channel blockers (non-dihydropyridine class) beta blockers Diuretics *efficacy in slowing the fall in the GFR (?)

ADA suggestion
modest

restriction of protein intake in diabetic individuals with microalbuminuria (0.81.0 g/kg per day) or macroalbuminuria (<0.8 g/kg per day). GFR <60 mL/min per 1.743 m2 consulation!

Estimated

Hemodialysis
As compared to nondiabetic individuals, hemodialysis in patients with DM is associated with more frequent complications

hypotension (due to autonomic neuropathy or loss of reflex tachycardia) more difficult vascular access accelerated progression of retinopathy.

Atherosclerosis is the leading cause of death in diabetic individuals on dialysis hyperlipidemia should be treated aggressively.

Renal Transplantation
from

a living related donor preferred therapy

Combined pancreas-kidney transplant offers the promise of normoglycemia and freedom from dialysis.

Thank you!