The basis of strict glucose control and the achievement of a favorable HgbAlc must involve the control of both fasting and post-prandial glucose levels. Most of the day is spent in the post-prandial state. The most important predictor of post prandial glycemia is the pre-prandial glucose. Glucose control in the United States is far from optimal with a minority of patients achieving either the ADA goal of 7.0% or the ACE/AACE goal of 6.5%. There is evidence that post-meal glucose has a better correlation with A1C than fasting glucose levels especially when the A1C is less than 8%. A reduced early insulin release leads to high postprandial glucose. The evidence that lowering Hgb A1C results in lower microvascular risk is substantial. The DCC T demonstrated a clear association, of retinopathy with A1C . The study also demonstrated that for the same Al C, intensive glucose control using short-acting insulin pre-meals was associated with reduced complications compared to conventional treatment without short acting insulin. Further evidence from the Kumamoto Study and the UKPDS confirm reduced microvascular complications with lower A1C levels. Elevated mealtime glucose is an unappreciated concern at all levels of A1C including A1C levels at normal or near normal values. Elevated mealtime glucose is of special concern in the elderly. There is strong epidemiologic evidence linking post challenge hyperglycemia to macro-vascular risk. These include the Rancho Bernardo study the Honolulu Heart Study, the Paris Prospective Heart Study, The Diabetes Intervention Study, and the DECODE Study. There are many other studies going back to the 1980s that relate post-challenge or post-prandial blood glucose to cardiovascular disease risk and mortality. Possible effects of acute hyperglycemia responsible for increased microvascular and macrovascular risk include endothelial dysfunction, increased oxidative load, a pro-inflammatory state, protein glycosylation and altered coagulation. There is evidence that oral glucose loading adversely affects endothelial function. Oxidative load in the form of reactive oxygen species is increased following a glucose challenge. The pro-inflammatory state relates to quintiles of dietary glycemic load as it does to the 2- hour post challenge glucose category. There is evidence that in intimal media thickness increases more with the 2 hour glucose than A 1С. In summary, post mealtime glucose spikes are to be prevented because lowering A1C reduces microvascular complications, A1C reflects post mealtime glucose as well as fasting plasma group glucose, elevated post-meal glucose is a highly prevalent issue and elevated blood glucose 2 hours after a glucose load is associated with increased risk of death independent of fasting blood glucose. The Epic- Norfork study raises questions as to the level of A1C associated with risk.

60?70% of all patients with Type 2 Diabetes Mellitus will ultimately require insulin therapy for the management of their diabetes. Irisulin may be used alone, or in combination with oral agents. The early use of insulin can be very important in decreasing the incidence of micro-vascular complications and in helping to delay the onset of macro-vascular complications. The United Kingdom Prospective Diabetes Study and the Kumamoto Study have shown the beneficial effects of good glucose control in type 2 diabetes mellitus. The DECODE study has related overall mortality to the level of glucose control and specifically to the postprandial glucose. The American Association of Clinical Endocrinologists has established a goal of 6.5% or less for HgbAlc. The appropriate use of insulin will allow us to achieve this goal without causing the patient any undue harm. There are many barriers to insulin therapy including psychological barriers of both the patient and the doctor, and unrealistic fears of both insulin therapy and therapy with self-administered injections. These barriers will be discussed as well as methods to overcome them. Insulin therapy is beneficial and has no long term adverse effects. The incidence of severe hypoglycemia is extremely low in type 2 diabetes. Weight gain is minimal. Insulin therapy by reducing glucose toxicity may also increase the effectiveness of oral anti-hyperglycemic agents. The physician taking care of patients with diabetes should be aggressive and should have no fears of initiating insulin therapy. Insulin dosage is flexible and good control is possible in most patients. The most common use of insulin in type 2 diabetes is as an add-on to oral agents if control with oral agents alone is unsatisfactory. Frequently this involves the use of a single dose of intermediate or long acting insulin or an insulin mixture in the evening. If control is not attained with a single dose, then the patient can be placed on an insulin mixture 2 or 3 times a day. An alternative would be a short acting insulin analogue prior to each meal with a longer acting insulin given 1 or 2 times a day. Titration schedules for insulin dosing will be presented. Insulin available in Russia will be listed along with some guidelines on using these insulins. Increasing the use of insulin and starting insulin earlier in type 2 diabetes will lead to better control of diabetes, increased patient compliance, and decreased long-term complications of diabetes mellitus.

The discovery of insulin changed the course of history in the treatment of diabetes. However, despite tremendous progress in insulin formulations and treatment strategies, insulin treatment still cannot fully prevent chronic complications and intensive insulin treatment to improve metabolic control, has often paralleled an increased risk of severe hypoglycemia. A cure for Type 1 diabetes should include: ? Restoration of self tolerance, to prevent recurrence of autoimmunity ? Restoration of physiologic metabolism by replacement of the biologic function (insulin producing cells) that was partially of completely impaired as a result of the disease process. ? Prevention of destruction of the new insulin producing cells by the recipient immune system in the absence of any treatment that could introduce an additional risk to the patient, which could be comparable to, or higher than the risk imposed by disease progression under exogenous insulin treatment. Pancreatic islets could be considered an ideal and more physiologic alternative to insulin, as they can restore metabolic control after transplantation, preventing the development of chronic complications. In fact, islets are capable of perfectly timed insulin release and can keep glucose levels in the normal range, functioning for an entire lifetime, if they are not destroyed by the recipient's immune system. Significant progress has been recently reported in the translational research approach towards the development of a cure for Type 1 diabetes. There is now strong evidence for the technical feasibility of human islet isolation and purification procedures. Proof of function of isolated human islets has been clearly established both in animal models and in pilot clinical trials of human islet allotransplantation in patients with surgical and Type 1 diabetes. Additional research in now needed to improve the current clinical results in terms of long term prevention of rejection and recurrence of autoimmunity, the development of safe, non diabetogenic immunomodulation strategies and ultimately the achievement of donor specific immune tolerance. If success will be achieved in these areas, then we will face the critical challenge of identifying sufficient and suitable sources of insulin producing tissue to treat the increasing number of patients who could benefit from this form of therapy and which would not be limited to Type 1 diabetes. That is why the work on xenogeneic islets, embryonic and adult stem cells, islet regeneration and proliferation, as well as engineering of insulin producing cells must be continued, to identify the most ideal source of insulin producing tissue that could be utilized on a large scale once the impediments and limitations of immunosuppression will be resolved.

Cardiovascular diseases (CVD) are responsible for 75% of the morbidity and mortality in patients with type 2 diabetes. Diabetes accelerates plaque formation and progression in coronary, cerebrovascular and peripheral arteries. Patients with diabetes obtain less benefit from invasive procedures such as angioplasty and coronary revascularization than do patients without diabetes. Survival following a cardiovascular event is lower in patients with diabetes, particularly in women. It is estimated that 50% of patients have CVD at the time of diagnosis with diabetes. This emphasizes the importance of early diagnosis and aggressive treatment of comorbidities and risk factors. Dyslipidemias in diabetes are characterized by elevated triglycerides, small dense LDL, and decreased HDL. The atherosclerotic process is associated with inflammatory changes with deposition of lipids in the arterial walls. Diabetes also accelerates this process by altering the structure and function of circulating lipoproteins. In a seven year study in a population in Finland, the incidence of myocardial infarctions (MI) in patients with diabetes without a prior MI was similar to patients without diabetes but with a previous MI. Thus, there is a linkage between diabetes and CVD at epidemiologic and pathophysiologic levels, and the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP-III) designated diabetes as a CVD risk equivalent. Treatment of LDL cholesterol is the first priority, followed by HDL and triglycerides: the goals are LDL < 100 mg/dL, HDL > 40 mg/dL in men or HDL > 50 mg/dL in women, and triglycerides < 150 mg/dL. Statins are the drugs of choice. Benefits of aggressive lipid management with statins have been shown in primary prevention studies (AFCAPS /TexCAPS, ASCOT) and secondary prevention studies (4S, CARE, LIPID, HPS) in patients with varying degrees of dyslipidemias and other risk factors. The Heart Protection Study (HPS) has shown that high risk patients benefit from statins regardless of the LDL levels. Other drugs, e.g., fibrates, nicotinic acid, bile acid sequestrants have a role in selected patients. A new class of drag, ezetimibe, blocks cholesterol absorption in the gastrointestinal tract: it is synergistic with the statins and effective as a single agent when statins are contraindicated. Aggressive therapy to treat diabetic dyslipidemias has been shown to reduce the risk of CVD.