Even relatively low doses of resveratrol--a chemical found in the skins of red grapes and in red wine--can improve the sensitivity of mice to the hormone insulin, according to a  new report.  As insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes, the findings "provide a potential new therapeutic approach for preventing or treating" both conditions, the researchers said.

Type-2-Diabetes is curable!

The phased plan of medication therapy of type 2 diabetes in the guidelines provides that, in addition to basic nutrition therapy, weight reduction and exercise a target HbA1c-value <6.5% will be achieved, otherwise an intervention from an HbA1c value 7.0% should be carried out.

In addition to the monotherapy with metformin with HbA1c failure to reach the target value can be a monotherapy with glibenclamide and glimepiride to be carried out. In a three-month cycle will then decided whether any other combination therapies with Acarbose, Glinides, glitazones or sulphonylureas will be carried out.

Should also below the HbA1c-value <7% after 3 months not be reached, an additional insulin therapy is required.

Since 26.1.2007, the glitazones pioglitazone in combination with insulin to be administered in patients with type 2 diabetes mellitus, their metabolism with insufficient insulin, and metformin, which because of the contra-indication or intolerance is inappropriate. By exogenous insulin supply may result in administration of pioglitazone, insulin sensitivity increased. This allows the insulin action to be strengthened, resulting in an improved HbA1c value in improved fasting and postprandial blood glucose values shows and, above all, a significant reduction in insulin dose possible.

In several studies have shown that in addition to the improved glycemic situation also an improvement of fat metabolism, blood pressure and less inflammation in the vascular wall could be demonstrated. The results of the PROactive study outcome shows throughout the observation period that the dose of insulin on average by more than 10% could be reduced. 9% of patients insulin could be completely removed. In practice benefit from the combination of insulin therapy + pioglitazone particularly patients with insulin resistance, high cardiovascular risk, impaired renal function and high insulin doses.

Insulin resistance and Insulin-secretion-disturbance - the sole cause of type 2 diabetes?

Currently there is a paradigm shift in the pathophysiological understanding of type 2 diabetes instead. The glucose think we have long been stored. Even when a diagnosis of diabetes mellitus type 2 is already a 50% loss of beta cell function.

In the pre-diabetes phase, we have already made a beginning of the beta cell dysfunction and the beginning of insulin resistance, even many years before the manifestation of diabetes - 7 to 12 years Pathomorphology mechanisms already in progress - the type 2 diabetes mellitus represent. In further career of type 2 diabetes mellitus is it to a chronic progressive beta cell dysfunction ultimately resulting in a further increase of hyperglycemia means. It is the main factor in the rise of plasma glucose and disease progression of Type 2 total.

Reduced beta cell mass by diabetes mellitus

When healthy, we have a 100% beta cell mass.
When Impaired Fasting glucose (IFG), there is already a 50% beta cell loss, while the diagnosis of diabetes mellitus.
Type 2 already an approximately 65% difference in beta cell mass is lost.
In type 1, we have over 90% of beta cell mass loss.
For this pathophysiological understanding out should therefore oral therapy of type 2 diabetes mellitus based.

Incretin Hormones

Important Incretin Hormones are today:

GLP-1: Glucagon like Peptid
GIP: Gastric inhibitory Polypeptide

Both regulate glucose homoeostasis effects on islet cell function.

When healthy metabolism stimulate Incretin hormones up to 70% insulin secretion after a fatty meal and rich in carbohydrates.

Incretins regulate glucose homoeostasis about their effect on islet cell function. It comes to a normal injection of a meal, the intestinal tract active GLP-1 and GIP released. This leads to a glucose-dependent insulin release into the beta cells as well as to increased peripheral glucose intake into the muscle and fat cells. At the same time, the alpha cells suppressed glucagon and glucose-dependent decreases to eliminate.

Effects of GLP-1 and GIP

In the foreground the regulation of glucose homoeostasis is GLP-1.

GLP-1 - Various effects

Type-2 diabetics have a reduced GLP-1-secretion, but still received GLP-1-function. Which makes it today in therapy with DPP-4-inhibitors Sitagliptin (Januvia) and GLP-1 analogues Exenidin-4/Byetta capitalize.

GLP-1 effect

GLP-1 as a stimulator effect of insulin secretion - glucose-dependent - is in type-2 diabetes received yet, but it comes through the DPP-4-enzyme (Dipeptidyl peptidase-IV) to a quick activation.

Current strategies to improve the therapeutic potential of GLP-1:

• Substances that the effect of GLP-1 initiate (Incretin mimetica)
• DPP-4-resistant GLP-1-derivatives
• For example, GLP-1-analogues, album-bound GLP-1
• Peptides, some of the glucose-regulating effects of GLP-1 launch.
• Exenatide (Byetta)
• Substances, the activity of endogenous GLP-1 extend. DPP-4 inhibitors - Sitagliptin (Januvia)

Physiologically will GLP-1 by the DPP-4-enzyme rapidly inactivated in about 2-4 minutes. This is the Evolution also provides exactly right, because we have only a short time need to appeal to a hyperglycaemic a beta stimulation of the GLP-1-beta receptors on the cell to reach. It uses the inhibition of this (Dipeptidyl peptidase-IV) enzyme to make a longer physiological GLP-1-effect in type 2 to reach.

GLP-1 lowers blood sugar only when glucose levels above 65 mg / dL or 3.6 mnol lies. There is hereby no hypoglycaemia and on the other side is also used for the current regulatory secretion of glucagon. DPP-4-inhibition by Sitagliptin (Januvia) highly. We know 9 Dipeptidyl-peptidases, the intestinal hormones break down. Through the selective inhibition e.g. by Sitagliptin (Januvia), we have a positive effect in terms of glucose-dependent glucose homeostasis-regulation by the beta cell.

The DPP-4 inhibitor Januvia (Sitagliptin) causes an approximately 24-hour action of GLP-1, by stimulation of insulin secretion only under:

• Hyperglycemia conditions, no hypoglycemia risk
• Inhibition of glucagon secretion
• Favorable effect on body weight (neutral) and reduction of appetite
• Effective and demand reduction in blood glucose
• Increase in beta cell mass
• Improvement of beta cell function (so far only, especially in animal experimental data)
• Minor side effects (DPP-4-inhibitors have a low incidence of hypoglycaemia and are well tolerated)
• Oral administration

GLP-1-analogues - Exenatide (Exendin 4)

When Exenatide is a synthetic version of the saliva protein Gilamonsters. It shows a 50% compliance with GLP-1 of the people. At the same time binds in vitro to known GLP1-beta receptors on the human. Inactivation by DPP-4 is not given. If the substance classes DPP-4-inhibitors and Incretin-mimetica opposite, however, noted that DPP-4-inhibitors administered orally once a day may be over-Incretin mimetica 2 x subcutaneous injection. The effect on GLP-1-mirror is at the DPP4 inhibitor Sitagliptin physiologically (high-physiological), while the Incretin-mimetica pharmacological effect and thus a higher concentration of GLP-1 effect of the blood-brain barrier and thus break the improved effect in terms of weight explain. The antibody formation is Incretin-mimetica exist, while DPP-4-inhibitors, of course missing. For Incretin-mimetica one sees at the beginning of a relatively high rate of nausea (40%), while DPP-4-inhibitors no side effects exist.

Use of DPP4 inhibitor Januvia and GLP-1-analogues (Byetta)
For diagnosis, there is already a 50% beta cell dysfunction and an approximately 65% difference in beta cell mass loss. As the type 2 diabetes mellitus is a chronic progressive disease acts as an expression of continuous beta cell dysfunction, this must be done in the therapy into account.  We need therefore a beta cell-protective therapy. The DPP-4-inhibitor (Januvia-Sitagliptin) should, after an initial metformin therapy early in combination be given. Furthermore, the combination of Januvia with glitazones possible. GLP-1-analogues (Byetta) are in combination with metformin and / or sulphonylureas admitted.

Through the GLP-1-analogue Byetta is the later use after initial metformin possibly combination therapy with sulphonylureas possible. It should be borne in mind that any of the sulfonylurea in combination with Byetta must be reduced to a possible to avoid hypoglycaemia. By combining Januvia with metformin, there is no hypoglycaemia, the same is true for Byetta with metformin.

By combining Januvia with metformin (DPP-4-inhibitor and GLP-1-analogue) Byetta could, for example, oral Antidiabetic others can be saved and, above all, the self-testing blood sugar dramatically prevented to be neglected, which is a favorable development would cost.

DIABETES

1. The three major categories of diabetes are type 1, type 2 and gestational diabetes. The latter occurs during pregnancy and is usually temporary (lasting only through pregnancy). Type 1 or type 2 diabetes can lead to serious complications from high glucose levels, including blindness, kidney disease and nerve damage, as well as vascular disease that can lead to amputations, heart disease and stroke. Gestational diabetes places a woman at greater risk of developing type 2 at some later time in her life.

2. The new term "pre-diabetes" describes an increasingly common condition in which blood glucose levels are higher than normal but not yet diabetic. Research supported by the US Department of Health and Human Services has shown that most people with this condition go on to develop type 2 diabetes within 10 years unless they make modest changes in their diet and level of physical activity, which can help them reduce their risks and avoid the debilitating disease. 

3. An estimated 20.8 million people in the US have diabetes, and nearly one third of those do not know they have it. Another 41 million people have pre-diabetes. Each year, about 1.3 million people are diagnosed with diabetes and more than 200,000 die from the disease.

4. Diabetes can strike at any age, but your risk for developing the disease increases as you age. According to the American Diabetes Association, diabetes increased by more than 60 percent from 1990 to 2001. The number of Americans with diabetes is growing by an alarming eight percent per year and the disease is the single most prevalent chronic illness in children. 

5. Key risk factors that you can control are obesity and sedentary lifestyle. If you are more than 20 percent above your ideal weight and rarely exercise, have your glucose tested and discuss a fitness plan with a health care professional. Losing even 10 pounds and exercising three times a week cuts your chances of developing diabetes.

6. Risk factors that you can't control are age, family history of diabetes and ethnic heritage. African Americans, Latino/Hispanics, Native Americans, Pacific Islanders and Asians are all more likely to develop type 2 diabetes (although Northern Europeans are more likely to contract type 1).

7. The best test for diabetes is one that measures fasting plasma glucose. The normal, nondiabetic range for blood glucose is from 70 to 100mg/dL. A level over 126 mg/dL usually means diabetes. A fasting plasma glucose test of 100 mg/dL or greater, but less than 126 mg/dL, indicates impaired fasting glucose or pre-diabetes, a frequent precursor to diabetes.

8. If you are diagnosed with diabetes, you can cut by half or more your risk of developing many of the associated complications-such as kidney disease and neuropathy-by following an intensive glucose management regimen, which includes frequently testing blood sugar, administering insulin (if applicable) on the basis of food intake and exercise, following a diet and exercise plan, and frequently consulting a health care team.

9. You should not smoke.

10. There is no cure for diabetes. However, it is almost always manageable, either with diet and exercise alone or with the addition of regular medical treatment. Diet and exercise also are key to reducing risk.

11. It's important to control the "ABCs" of diabetes: A for the A1C test (hemoglobin A1C); B for blood pressure and C for cholesterol. The National Institutes of Health and the American Diabetes Association recommend the following target numbers: A1C: below 7 (an average blood glucose of 150); blood pressure below 130/80; and LDL cholesterol below 100. Talk to your health care professional about your "ABC" targets and your blood pressure (keeping it at less than 130/80) and LDL cholesterol (less than 100 mg/dL is optimal for individuals with diabetes; less than 70 mg/dL is desirable for those with both diabetes and heart disease).