The Meglitinides
The meglitinides are more properly referred to as the glinides because repaglinide and nateglinide are not members of the same chemical class. Repaglinide is a benzoic acid derivative and nateglinide is a phenylalanine derivative. The glinides specifically target postprandial hyperglycemia, and, compared with sulfonylureas, have less risk of hypoglycemia and less continuous stimulation of the P-cells. The glinides are designed to return insulin levels to baseline between meals and to stimulate...
Triple Oral Agent Therapy
Although triple oral agent therapy is effective when all three agents are used synergis-tically, little data exists with regard to triple-agent therapy. Before its withdrawal from the market, the addition of troglitazone to patients with type 2 diabetes poorly controlled with sulfonylureas and metformin produced an additional 1.3 decrease in hemoglobin A1-C. Similar results have been reported with pioglitazone and rosiglitazone 21 . Adding an a-glucosidase inhibitor to metformin and a...
Risk Determinants
The ATP-III has upgraded diabetes to a coronary artery disease equivalent. Patients with coronary artery disease risk equivalents carry a risk of major coronary events of greater than 20 in the next 10 years. In addition to diabetes, the other risk equivalents are as follows 1. Symptomatic carotid artery disease. 2. Peripheral vascular disease. The metabolic syndrome is soon to be elevated to a coronary artery disease equivalent. The presence of multiple risk factors can increase risk to...
aGlucosidase Inhibitors and Sulfonylurea
Introduced in 1996, miglitol and acarbose are currently approved for monotherapy and in combination with sulfonylureas, insulin, metformin, and the TZDs. Miglitol and acarbose do not cause malabsorption but delay the digestion of carbohydrates with subsequent absorption shifted to the more distal parts of the small intestine and colon. Miglitol and acarbose can be very effective in blunting postprandial plasma glucose elevations, allowing the P-cells enough time to increase insulin secretion....
ORAL AGENT CLASSES Sulfonylureas
Sulfonylureas are indicated when hyperglycemia cannot be controlled with exercise, diet, and therapeutic lifestyle changes. They bind to a specific receptor on the pancreatic P-cells that enhances the effect on glucose lowering resulting from a closure of the potassium-dependent adenosine triphosphate K-ATP channel. Glimepiride Amaryl binds to a different protein than the other sulfonylureas, but on the same site as the potassium channel. The subsequent reduction in plasma glucose results in...
REFERENCES Wze
1. Steiner G. 200 Lipid intervention trials in diabetes. Diabetes Care 23 Suppl 2 B49-B53. 2. Mykkanen L, Laakso M, Penttila I, Pyorala K. 1991 . Asymptomatic hyperglycemia and cardiovascular risk factors in the elderly. Atherosclerosis 88 153-161. 3. Best JD, O'Neal DN. 2000 Diabetic dyslipidemia, current treatment and recommendations. Drugs 59 1101-1111. 4. Lamarche B, Tchernof A, Moorjani S, et al. 91997 Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic...
REFERENCES Syu
1. Luna B, Feinglos MN. 2001 Oral agents in the management of type 2 diabetes mellitus. Am Fam Physician 63 1747-1756. 2. Mudaliar S, Henry RR. 2001 New oral therapies for type 2 diabetes mellitus the glitazones or insulin sensitizers. Annu Rev Med 52 239-257. 3. Ahmann AJ, Riddle MC. 2000 Oral pharmacological agents. In Medical Management of Diabetes Mellitus. New York, NY Marcel Dekker, pp. 267-283. 4. DeFronzo RA. 1999 Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 133...
Diabetes Care 537-544
1. Olson DE, Norms SL. 2004 Diabetes in older adults. Overview of AGS guidelines for the treatment of diabetes mellitus in geriatric populations. Geriatrics 59 18-24. 2. Pietropaolo M, Le Roith D. 2001 Pathogenesis of diabetes our current understanding. Clin Cornerstone 4 1-16. 3. Ramlo-Halsted BA, Edelman SV. 1999 The natural history of type 2 diabetes. Implications for clinical practice. Prim Care 26 771-789. 4. Engelgau MM, Narayan KM, Herman WH. 2000 Screening for type 2 diabetes. Diabetes...
Blood Pressure Control
Interestingly, blockage of the angiotensin II type I receptor has been shown to improve endothelial function and diminish endothelial adhesiveness. Angiotensin II promotes sodium retention, vasoconstriction, slows progression of glomerular injury at the renal level, and induces cardiac and vascular myocyte hypertrophy, fibromuscular proliferation, and endothelial cell apoptosis 22 . With this in mind, the concept of combined therapy with angiotensin-converting enzyme ACE inhibitors and...
REFERENCES Ksd
1. Curb JD, Pressel SL, Cutler JA, et al. 1996 Effect of diuretic based antihypertensive treatment on cardiovascular risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA 276 1886-1892. 2. United Kingdom Prospective Diabetes Study UKPDS Group. 1998 Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. UKPDS 38 . BMJ 317 703-713. 3. Hansson L,...
Novel Therapeutics
Implantable insulin pumps have not yet been approved for use in the United States. Generally, patients using these pumps are more satisfied with their treatment and experience less weight gain. This technique delivers insulin directly into the abdominal cavity, closely resembling normal insulin physiology and production even more than subcutaneous injections. This technology, along with an implantable glucose sensor, may provide an important breakthrough and advance in insulin-pump therapy....
Diabetic Neuropathy
Diabetic neuropathy afflicts up to 70 of patients with type 2 diabetes. Diabetic neuropathy does not represent one distinct disease but rather an adverse group of conditions that effect the peripheral nervous system, attacking the peripheral, proximal, and autonomic nerves, and causing both focal and systemic disease. Patients with diabetic neuropathy may have pain or impaired sensation in the feet and hands, slow digestion, carpal tunnel syndrome, or impaired cardiovascular responses 17 ....
REFERENCES Mrb
1. Bhaskarabhtia KV, Birrer R. 2004 Physical Activity and Type 2 diabetes tailoring exercise to optimize fitness and glycemic control. Physician and Sports Medicine 32 13-17. 2. Tuomilehto J, Lindstrom J, Eriksson JG, et al. 2001 Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344 1343-1350. 3. Zinman B, Ruderman N, Campaigne BN, Devlin JT, Schneider SH, American Diabetes Association. 2003 Physical activity exercise and...
Shortacting Insulins And Their Analogs
The first genetically altered rapid-acting analog insulin, lispro Humalog , was formed by switching lysine and proline at the 28 and 29 position of the P-chain in the insulin molecule. This insulin was approved in 1996. The insulin aspart NovoLog , formed by substituting aspartic acid for proline at the 28 position of the P-chain, was introduced in 2000. Both lispro and aspart analogs have similar rapid onsets of action of 5-15 minutes, which allows doses at, or even just after, a meal with...
Longacting Insulins
Ultralente is usually given before the evening meal or at bedtime, has a duration of action that is quite variable 13-18 hours ,and has variable peaking times between 8 and 14 hours. Ultralente has fallen into disfavor because of the peaks and valleys in its coverage. Glargine Lantus is an analog insulin with significant advantages over the Ultralente preparation. Glargine has an onset of action of 1-2 hours, is virtually peakless, and has a duration of action of 24 hours. Glargine is produced...
Combination Therapy
The ADA recommends the use of dihydropyridine CCBs only in combination with but not instead of ACE inhibitors or ARBs for patients with diabetes and elevated blood pressure. The combination therapy approach to hypertensive management in the patient with diabetes is extremely appealing. The increased efficacy of the combination over monotherapy has been well-established. The decreased side effects with combination therapy along with the increased efficacy and improved patient compliance make it...