Diabetes Mellitus: Pathophysiology

PATHOPHYSIOLOGY OF DM

IMPAIRED INSULIN SECRETION

A pancreas with normal Beta cell function is able to adjust insulin production to maintain normal blood glucose levels.
Hyperinsulinemia or high blood levels of insulin is an early finding of T2 DM.
More insulin is secreted to maintain normal blood glucose levels until eventually the pancreas can no longer produce sufficient insulin.
Impaired Beta cell function results in reduced ability to produce a first-phase insulin response sufficient to signal the liver to stop producing glucose after a meal.
As DM progresses, large numbers of patients with T2DM eventually loses all beta cell function and require exogenous insulin to maintain the blood glucose levels.

INSULIN RESISTANCE

Insulin resistance is the primary factor that differentiates T2DM from other forms of diabetes.
Insulin resistance maybe present for several years prior to the diagnosis of DM.
Insulin resistance occurs more significantly in skeletal muscles and liver.
Insulin resistance in the liver poses a double threat because the liver becomes nonresponsive to insulin for glucose uptake and hepatic production of glucose after a meal does not cease which leads to elevated fasting and post-meal glucose levels.

IMAPIRED GLUCAGON SECRETION

Glucagon is the counter regulatory hormones produced by the beta cells that raises blood glucose levels.
The release of insulin and the inhibition of glucagon is glucose stimulated.
Most patients with a 10–20-year history of T1DM have lost their ability to release glucagon, which increases their risk of hypoglycemic unawareness.

GLUCAGON LIKE PEPTIDE AND GIP IMAPIRED

People with T2DM have impaired phase 2 insulin release, and some have impaired glucagon-like peptide (GLP-Q) and glucose-dependent insulinotropic polypeptide (GIP) release, which further reduces the release of insulin.

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Diabetes Mellitus: Types!

TYPES OF DIABETES MELLITUS 1. TYPE1 DM Type 1 DM is usually diagnosed before age 30 years, but it can develop at any age. T1DM is an autoimmune disease in which insulin producing B-cells are destroyed. The presence of Human Leucocyte Antigens (HLAs ) is associated with the development of T1DM. In addition, these individuals often develop Islet cell antibodies , Insulin Autoantibodies or Glutamic Acid decarboxylase autoantibodies . At the time of development of diagnosis of T1DM, it is usually believed that most of the patients have 80-90%loss of beta cells. The remaining beta cells function at the diagnosis creates a " HONEYMOON PERIOD" during which the blood glucose levels are easier to control, and smaller amounts of insulin are required. after this, the remaining beta cells function is completely lost, and the patients become completely deficient of insulin and hence require exogenous insulin. 2. TYPE1.5 DM: Also referred as Latent autoimmune diabetes in Adults (LAD)

Diabetes Mellitus: Pharmacotherapy- Gliptins and a-Glycoside Inhibitors!

PHARMACOTHERAPY: Medications classifications include: Sulfonyl Urea's Nonsylfonylurea Secretagogues (a-Glinides) Biguanides Thiazolidinediones a-Glucosidase Inhibitors Dipeptidyl Peptidase-4 Inhibitors (Gliptins) Sodium-glucose co-transporter (SGLT) Inhibitors Central-Acting Dopamine Agonists Bile Acid Sequestrants Insulin therapy 5. a-GLUCOSIDASE INHIBITORS Acarbose and Miglitol are a-glucosidase inhibitors currently approved in the United States. Mechanism of Action: An enzyme that is along the brush border of the intestine cells called a-glucosidase; breaks down the complex carbohydrates into simple sugars, resulting in absorption. The a-glucosidase inhibitors work by delaying the absorption of carbohydrates from the intestinal tract, which reduces the rise in postprandial glucose levels. Therapy: As a monotherapy , a-glucosidase inhibitors primarily reduce post-prandial glucose excursions. Clinical Use: FPG concentrations have been decreased by 40-50mg/dL and A1c level

GASTRO-ESOPHAGEAL REFLUX DISEASE (GERD)!

MANAGEMENT OF GASTRO-ESOPHAGEAL REFLUX DISEASE "GERD refers to the endoscopically determined esophagitis or endoscopy-negative reflux disease" . "GERD is the term used to describe any symptomatic clinical condition or histopathological alteration resulting from episodes of reflux of acid, pepsin and occasionally, bile into the esophagus from the stomach". Patients with uninvestigated "reflux-like" symptoms should be managed as patients with uninvestigated dyspepsia. There is currently no evidence that H.pylori should be investigated in patients with GERD. Symptoms: Heartburn is the characteristic symptom of GERD. Acid regurgitation Dysphagia Belching Upper abdominal discomfort Bloating and postprandial fullness Chest pain Hoarseness Cough Complications include: Esophageal ulceration Formation of specialized columnar-lined esophagus at the gastro-esophageal junction known as Barretts Esophagus . Mechanism of Acid Reflux: The mechanism of acid reflux is mu

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