Pengobatan dm biasanya karena komplikasi microvaskular dan macrovaskular. Komplikasi yg melibatkan kematian pada dm tipe 2 adalah penyakit jantung.

Komplikasi dm, korelasi dengan gula darah puasa. Dx: 1) Gula darah post prandial, >200mg/dl 2) Gula darah sewaktu , >200mg/dl + gejala klinis 3p 3) Gula darah puasa, >126mg/dl Istilah: Gula darah pp terganggu, 100-125mg/dl Glucose intolerance 140-200mg/dl Th dm 1) Gizi 2) Excercise Penyebab dm tipe 2 peripheral insulin resistance, impaired regulation of hepatic glucose production, and declining -cell function, eventually leading to -cell failure. Nefropati Neuropati Retinopati

Insulin +Transmembranous transport + glucose sensor.. Glucose sensor menghasilkan glukokinase. metabolism with the insulin secretory apparatus masalah pada glucose transport xboleh masuk otot sbb insulin x cukup All currently available sulfonylureas bind to specific receptors on -cells, resulting in closure of potassium ATP channels. As a result, calcium channels open, leading to an increase in cytoplastic calcium that stimulates insulin release (74). A newer sulfonylurea, glimiperide, given in doses of 1, 4, or 8 mg

Repaglinide is a new agent that binds to pancreatic -cells and stimulates insulin release. It is structurally different from sulfonylureas and binds to a nonsulfonylurea receptor Thiazolidenediones appears to act by binding to the peroxisome proliferator activator receptor- (95, 96). This nuclear receptor influences the differentiation of fibroblasts into adipocytes and lowers free fatty acid levels -Glucosidase inhibitors Members of this class act by slowing the absorption of carbohydrates from the intestines and thereby minimize the postprandial rise in blood glucose (104). Gastrointestinal side-effects require gradual dosage increments over weeks to months after therapy is initiated. Serious adverse reactions are rare, and weight gain may be minimized with this therapy. Acarbose, the agent of this class in clinical use, may be added to most other available therapies (105). Insulin therapy is indicated in the treatment of type 2 diabetes for initial therapy of severe hyperglycemia, after failure of oral agents, or during perioperative or other acute hyperglycemic states COMPLICATIONS an autoimmune destruction of pancreatic beta cells.

absolute insulin deficiency and no longer produces insulin.

Triggered by an environmental event, such as a viral infection. Genetically The onset of type 1 diabetes is usually abrupt. before the age of 30 years, but may be diagnosed at any age. normal weight or are thin in stature.

absolutely dependent on exogenously administered insulin for survival. highly susceptible to diabetic ketoacidosis. Because the pancreas produces no insulin, glucose cannot enter cells and remains in the bloodstream. Because of hyperglycemia and the fact that body do not produce insulin, gluconeogenesis occurs to make sure of insulin production. fat is broken down through lipolysis, releasing glycerol and free fatty acids. Glycerol is converted to glucose for cellular use. Fatty acids are converted to ketones, resulting in increased ketone levels in body fluids and decreased hydrogen ion concentration (pH). Ketones are excreted in the urine, accompanied by large amounts of water. The accumulation of ketones in body fluids, decreased pH, electrolyte loss and dehydration from excessive urination, and alterations in the bicarbonate buffer system result in diabetic ketoacidosis (DKA).

 Untreated DKA can result in coma or death. initially diagnosed with the disease following a hospital admission for DKA. stress or infection may precipitate DKA. DKA results from poor daily glycemic control (remain severely hyperglycemic for several days or longer due to inadequate insulin administration or excessive glucose intake).
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DM TYPE 2 acquired risk factors for type 2 diabetes include obesity, advancing age, and an inactive lifestyle. (PATHOPHYISIOLOGY) the following three disorders: (1) peripheral resistance to insulin, especially in muscle cells; (early stage) (2) increased production of glucose by the liver; and, (3) altered pancreatic insulin secretion. (later stage) Increased tissue resistance to insulin generally occurs first and is eventually followed by impaired insulin secretion. The pancreas produces insulin, yet insulin resistance prevents its proper use at the cellular level. Glucose cannot enter target cells and accumulates in the bloodstream, resulting in hyperglycemia. The high blood glucose levels often stimulate an increase in insulin production by the pancreas; thus, type 2 diabetic individuals often have excessive insulin production (hyperinsulinemia) masih awal. Over the years, pancreatic insulin production usually decreases to below normal levels. In addition to hyperglycemia, type 2 diabetic patients often have a group of disorders that has been called "insulin resistance syndrome" or syndrome X. Obesity contributes greatly to insulin resistance, even in the absence of diabetes. In fact, weight loss is a cornerstone of therapy type 2 diabetes are unaware of their disease. type 2 diabetic patients are diagnosed, diabetic complications have already begun. Long periods of severe hyperglycemia may result in hyperosmolar nonketotic acidosis

Hyperglycemia results in the urinary excretion of large amounts of glucose, with attendant water loss. If fluids are not replaced, the dehydration can result in electrolyte imbalance and acidosis.

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Gestational diabetes As with type 2 diabetes, the pathophysiology of gestational diabetes is associated with increased insulin resistance
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Increase glucose tolerance and increase fasting glucose IGT and IFG are not considered to be clinical entities; rather, they are risk factors for future diabetes. The pathophysiology of IFG and IGT is related primarily to increased insulin resistance whereas endogenous insulin secretion is normal in most patients.
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The major cause of the high morbidity and mortality rate as with diabetes is a group of microvascular and macrovascular complications affecting multiple organ systems.

People with diabetes have a greatly increased risk for blindness, kidney failure, myocardial infarction, stroke, necessary limb amputation, and a host of other maladies.

Other disorders (such as hypertension and dyslipidemia) commonly seen in people with diabetes increase the risk for microvascular and macrovascular complications.

There may also be genetic determinants of risk for diabetic complications.

The vascular complications result from

1)atherosclerosis and 2)microangiopathy. Increased lipid deposition and atheroma formation is seen in the larger blood vessels, along with increased thickness of arterial walls. Proliferation of endothelial cells, alterations in endothelial basement membranes, and changes in the function of endothelial cells induce microvascular damage. While poor glycemic control is clearly a major risk factor for complications, not all poorly controlled diabetic patients develop complications. Conversely, some individuals develop complications despite relatively good glycemic control.

Hyperglycemia plays a major role in both microvascular and macrovascular disease. Hyperglycemia dramatically alters the function of multiple cell types and their extracellular matrix. This results in structural and functional changes in the affected tissues.

Research has recently focused on lipoprotein metabolism and on th (gluconeogenesis) e glycation of proteins, lipids, and nucleic acids as possible common links between the different diabetic complications. ALDOSE REDUCTASE Aldose reductase is the initial enzyme in the intracellular polyol pathway. This pathway involves the conversion of glucose into glucose alcohol (sorbitol). High glucose levels increase the flux of sugar molecules through the polyol pathway, which causes sorbitol accumulation in cells. Osmotic stress from sorbitol accumulation has been postulated as an underlying mechanism in the development of diabetic microvascular complications, including diabetic retinopathy. sugar alcohol accumulation has been linked to microaneurysm formation, thickening of basement membranes, and loss of pericytes

OXIDATIVE STRESS

The function of cell membranes is determined largely by their phospholipid bilayers; thus, changes in lipid metabolism can have major effects on cell function. The oxidation of circulating low-density lipoprotein (LDL) in hyperglycemic individuals increases oxidant stress within the vasculature. This induces chemotaxis of monocytes and macrophages into the vessel walls, where oxidized LDL causes changes in cellular adhesion and increased production of cytokines and growth factors. VASCULAR ENDOTHELIAL GROWTH FACTOR 1)smooth-muscle cell proliferation increases vessel wall thickness. Other changes include increased 2)atheroma formation and development of 3)microthrombi in large blood vessels and alterations permeability and endothelial cell function in the microvasculature. AGES The glycation of proteins, lipids, and nucleic acids increases with sustained hyperglycemia. The microvasculature of the retina, renal glomerulus, and endoneurial areas, as well as the walls of the larger blood vessels, accumulate deposits of glycated proteins called advanced glycation end products (AGEs). AGEs is much greater in individuals with diabetes, especially when the diabetic state is poorly controlled. AGE formation alters the structural and functional properties of the affected tissues. In the walls of the large blood vessels (INTRAVASCULAR), AGE-modified collagen accumulates, 1)thickening the vessel wall and 2)narrowing the lumen. AGE-modified arterial collagen 3)immobilizes circulating LDL, contributing to 4)atheroma formation. in vascular

Accumulation of AGEs causes increased basement membrane thickness in the microvasculature of the retina and around the nerves and increased thickness of the mesangial matrix in the glomerulus. The cumulative effect of these changes is a progressive narrowing of the vessel lumen and 5)decreased perfusion of affected tissues. AGE formation also has major effects at the cellular level (INTRACELL), causing modifications in extracellular matrix components and changes in cell-to-matrix and matrix-to-matrix interactions. The binding of AGEs to specific cellular receptors that have been identified on the surface of smooth-muscle cells, endothelial cells, neurons, monocytes, and macrophages results in 1)increased vascular permeability and thrombus formation, 2)proliferation of smooth muscle in vessel walls, and 3)phenotypic alteration in monocytes and macrophages. 4)hyper-responsiveness of monocytes and macrophages upon stimulation, with resultant increases in the production of proinflammatory cytokines and certain growth factors). 5)chronic inflammatory process in the formation of atherosclerotic lesions. 6)increased tissue destruction in response to antigens such as the bacteria These changes in protein and lipid metabolism, induced by the elevated plasma glucose levels characteristic of diabetes, may thus provide a common connection between the various diabetic complications.

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microvascular Diabetic retinopathy (most common) *occurs sooner in dm type 1 than 2* Dot haemorrhages Hard exudates (lipid accumulation) Red dots (microaneurysms) Greyish part (retinal edema) Cotton wool spots (proliferation of new blood

macrovascular Type 2 diabetes typically occurs in the setting of the metabolic syndrome, which also includes abdominal obesity, hypertension, hyperlipidemia, and increased coagulability of stroke and cerebrovascular disease, as in coronary artery disease

vessel which can cause vitreous haemorrhages) Thx: laser photocoagulation Diabetic nephropathy Proteinuria : >500mg/24 hrs Microalbuminuria: 30299mg/24hrs increased glomerular basement membrane thickness, microaneurysm formation, mesangial nodule formation (KimmelsteilWilson bodies), thx: ACE and ARBs ( works only for dm type 2) Peripheral neuropathy in diabetes may manifest in several different forms, sensory, focal/multifocal, and autonomic neuropathies. More than 80% of amputations occur after foot ulceration or injury Chronic sensorimotor distal symmetric polyneuropathy. experience burning, tingling, and electrical pain, but sometimes they may experience simple numbness Pure sensory neuropathy Mononeuropathies median, ulnar, and radial nerves severe pain and muscle weakness and atrophy, usually in large thigh muscles. Diabetic autonomic neuropathy gastroparesis, constipation, diarrhea, anhidrosis, bladder dysfunction, erectile dysfunction, exercise intolerance, resting tachycardia, silent ischemia, and even sudden cardiac death.

Diabetic neuropathy

Thx: Amitriptyline, imiprimine, paroxetine, citalopram, gabapentin, pregablin, carbamazepine, topiramate, duloxetine, tramadol, and oxycodone have all been used to treat painful symptoms, but only duloxetine and pregablin possess official indications for the treatment of painful peripheral diabetic neuropathy