A study of Hispanic African Americans shows that insulin resistance and beta-cell dysfunction independently predict diabetes.

Central obesity, however, was not significantly associated with diabetes independently of insulin sensitivity or secretion, suggesting “a portion of the association of visceral adipose tissue with diabetes mellitus operates through these disorders,” report the authors.

Anthony Hanley (University of Toronto, Canada) and colleagues investigated the association of directly measured visceral and subcutaneous adiposity, insulin sensitivity, and beta-cell dysfunction with the 5-year incidence of Type 2 diabetes in 1230 Hispanic??” and African??”American participants who were free of diabetes at baseline.

The study cohort was from the Insulin Resistance Atherosclerosis (IRAS) Family Study, which is assessing three generations of family members to determine how many of the precursors to adult-onset Type 2 diabetes and obesity are inherited.

Fat mass in the abdominal region was measured by computed tomography. Insulin sensitivity and the acute insulin response (AIR), a measure of insulin secretion, were determined from frequently sampled intravenous glucose tolerance tests.

Incident Type 2 diabetes was diagnosed in 90 participants over 5 years. These individuals had significantly lower baseline insulin sensitivity and AIR, as well as higher glucose and insulin concentrations, and were more likely to have had impaired fasting glucose at baseline than those who did not develop the condition.

In individual models, both insulin sensitivity and AIR were inversely associated with Type 2 diabetes incidence after adjustment for baseline variables including age, gender, ethnicity, center, and impaired fasting glucose, with odds ratios of 0.53 and 0.22, respectively. Visceral and subcutaneous adipose tissue were both positively associated with Type 2 diabetes, with odds ratios of 1.68 and 1.49, respectively.

The association of visceral adipose tissue with diabetes was notably stronger in women than men.

In models including both visceral and subcutaneous adipose tissue, only visceral adiposity was a significant risk factor for diabetes.

Finally, in a model examining the joint effects of visceral and subcutaneous adipose tissue and insulin sensitivity/secretion, insulin sensitivity and AIR were significant predictors of Type 2 diabetes, but associations with visceral and subcutaneous adiposity were no longer significant.

“The detrimental effect of reduced insulin sensitivity and secretion is independent of directly quantified visceral and subcutaneous adipose tissue, and is present in multiple high-risk populations, including African and Hispanic Americans,” they conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Emodin, a natural compound that can be extracted from several Chinese herbs, has been shown to inhibit the enzyme 11b-Hydroxysteroid dehydrogenase type 1 (11?-HSD1) in mice, suggesting a potential therapeutic target for treating Type 2 diabetes and other metabolic conditions.

The 11?-HSD1 enzyme stimulates glucocorticoid secretion, which, in turn, has been linked to insulin resistance and Type 2 diabetes when present in excess. Therefore inhibition of 11?-HSD1 provides a potential pathway for treating Type 2 diabetes.

Ying Leng and colleagues from the Chinese Academy of Sciences in Shanghai, China, screened a collection of phytocompounds for their ability to inhibit 11?-HSD1. Emodin, an anthraquinone derivative mostly from Rheum palmatum, was found to be the most potent selective 11?-HSD1 inhibitor.

The team tested the inhibitory activity of emodin in vitro, against human and mouse recombinant 11?-HSD1 generated in HEK-293 cells, and in vivo, in C57BL/6J mice with prednisone- or dexamethasone-induced insulin resistance. The effect of emodin on metabolic abnormalities in diet-induced obese (DIO) mice was also assessed.

Emodin was a significant inhibitor of human and mouse recombinant 11?-HSD1, with IC₅₀ scores of 186 and 86 nM, respectively. In addition, it was found to reverse prednisone-, but not dexamethasone-induced insulin resistance in C57BL/6J mice.

“Dexamethasone is a synthetic cortisol analogue, whereas prednisone is a synthetic cortisone analogue and needs to be catalysed by 11?-HSD1 in the liver to convert it into its active metabolite, prednisolone,” explain Leng et al.

“Therefore, the finding that emodin prevented prednisone-induced insulin resistance confirmed that chronic administration of emodin can inhibit hepatic 11?-HSD1 activity in vivo.”

As reported in the British Journal of Pharmacology, the researchers also found that oral administration of emodin lead to improved lipid metabolism and insulin sensitivity in DIO mice, as well as lower hepatic phosphoenolpyruvate carboxykinase, glucose-6-phosphatase mRNA, and blood glucose.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Study findings show that women with previous gestational diabetes mellitus (GDM) have increased prevalence of non-alcoholic fatty liver disease (NAFLD) compared with women who have not experienced GDM.

NAFLD is known to be common in patients with Type 2 diabetes, but whether women at high risk for Type 2 diabetes, such as those who have previously experienced GDM, are at increased risk is less clear.

For the purposes of this study, Shareen Forbes (University of Edinburgh, UK) and colleagues recruited 110 women with previous GDM (within previous 10 years) and 113 without prior GDM (controls). They had liver ultrasound examinations, blood tests to assess liver function, lipid, and glucose levels, and had anthropometric factors measured.

As reported in the journal Diabetologia, prevalence of NAFLD was significantly greater in women with prior GDM than controls, at 38% versus 17%.

Body mass index (BMI) was not significantly different between the two groups. However, women with previous GDM had significantly higher fasting (5.3 vs 5.1 mmol/l) and 2-hour glucose (6.8 vs 5.8 mmol/l) concentrations following an oral glucose tolerance test (75 g) than controls.

In addition, GDM women were more likely to have dyslipidemia, lower insulin sensitivity, and higher insulin secretion than controls.

“As these women are at significant risk of Type 2 diabetes, this result may be consistent with NAFLD preceding Type 2 diabetes in this cohort,” write Forbes et al.

They add: “Diminished insulin sensitivity and raised alanine aminotransferase activity may all contribute to the development of NAFLD in these women.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Treatment with glimepiride slows progression of carotid intima-media thickness (IMT) to a greater degree than glibenclamide in patients with Type 2 diabetes, suggest results from a small observational study.

“Recent studies reported that glimepiride increased plasma adiponectin levels and decreased plasma tumor necrosis factor-? levels in Type 2 diabetics,” the say researchers.

In addition, “in animal models, glimepiride has been shown to reduce atherosclerotic lesions as compared to conventional sulfonylureas [eg, glibenclamide].”

Naoto Katakami (Osaka University, Japan) and colleagues therefore followed-up 40 Type 2 diabetes patients, aged 65.2 years on average - 20 treated with glimepiride and 20 with glibenclamide - for 3 years to assess the potential impact on subclinical progression of atherosclerosis, as measured by carotid IMT.

They found that patients treated with glimepiride had a significantly slower progression of carotid IMT over the study period than those treated with glibenclamide, at -0.044 versus +0.077 mm/year.

The researchers say that these results agree with those of a previous clinical trial that showed a significant improvement of brachial-ankle pulse wave velocity and augmentation index in patients treated with glimepiride who had switched from glibenclamide.

“Since glimepiride has been shown to improve insulin sensitivity and modulate plasma adipocytokine levels in diabetic patients, these actions may explain the mechanisms of its beneficial effect on the progression of carotid IMT,” say Katakami et al.

They conclude: “We consider this study not conclusive but hypothesis generating. Larger replication studies should be designed with appropriate sample size calculations and our results could provide a rationale to conduct such studies.”

The results of this study are published in the journal Diabetes Research and Clinical Practice.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

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There is no magic answer to losing weight or keeping it stable … unfortunately. Weight loss or weight gain really depends on balancing the calories you eat against the calories you use in your day to day activities. So, if you eat more than you use, you will definitely put on weight.

When you received your type 2 diabetes diagnosis, I am sure you were told about a healthy lifestyle program which included an eating plan with reduced amounts of refined carbohydrate or sugar, and better dietary choices. I also feel certain you were encouraged to add exercise to your program to help bring your weight under control and as an aid in reducing your blood sugar levels.

Any increase in physical activity increases your insulin sensitivity and reduces your risk of heart attack. How much exercise do you need to do to get good results? Various reports have led the US Surgeon General and the American College of Sports Medicine to suggest thirty minutes of vigorous exercise almost every day, preferably every day. If you find this doesn’t work for you, simply walking briskly each day for approximately forty-five minutes can lower your insulin resistance and help greatly with your weight loss.

Before increasing the amount of exercise you are doing at present check with your health care provider. Have a thorough physical examination if you:

• are more than thirty years of age
• have not exercised for the past six or more months
• have any cardiovascular condition, eg. heart disease, high blood pressure, or have experienced fainting or weakness of any description
• have had a heart attack
• have asthma or any lung disease
• have arthritis
• have insulin-dependent diabetes … your insulin dose will need to be adjusted

Exercise is great but you can’t just do it for a bit, then stop and expect your type 2 diabetes and insulin resistance to be cured. Once you stop exercising on a regular basis, your insulin levels will go right back up to their old levels. There are studies that show the beneficial effects of exercise only last for about sixty hours.

Any exercise is better than none though … a single exercise session can increase the efficiency of your insulin both during exercise and for as much as two days afterward, even if you are not physically fit. If you are fit and exercise on a regular basis, your results will be better still.

I’m working with an athlete who has recently been diagnosed as a diabetic and is training for an Ironman. He is also new to triathlons and all the training and logistics that come with it.

Last week I got an email from him about two problems with his diabetes management:

?? 1. High glucose levels on his early bike sessions

?? 2. Hypoglycemia during swim workouts done at lunch time

1) Hyperglycemia early in the morning is very common in diabetics. Also known as the Dawn Phenomenon, it is the result of decreased insulin sensitivity and changes in the levels of various hormones in the early morning hours (GH, Cortisol, Glucagon), which can lead to the overproduction of glucose by the liver and to the underutilization of glucose by peripheral tissues.?

Since the bike workouts are only about one hour, there is no need to have a big breakfast before these. So he was instructed to get a big breakfast after those workouts, taking a couple of extra ultra-fast insulin with it, and check blood glucose levels 2 hours after the meal to make sure it was all absorbed.

2) Hypoglycemia during swim workouts done at lunch time

For the second issue, there is also a link between the situations that are causing the hypoglycemia during the swim.

First of all, swimming brings with it a higher metabolism rate and a higher number of muscles involved in the work compared with running or biking. When you swim you are using many small muscles, which make the glycogen consumption a bit higher than during biking or running, thus making swimming the discipline that causes a bigger drop in blood glucose levels for the first hour of training.

Another reason is that on some days this athlete is training in the morning (when the dawn phenomenon occurs) as well. So by the time he gets in the pool, not only is his metabolism higher but his insulin sensitivity is high too.

I remember that back in my training days it didn’t matter how high my blood glucose levels were before a workout - if I didn’t eat anything before the session I would end up with a hypo.

The advice for my athlete was:

1. If blood glucose level is >180: Take a bottle of maltodextrin/sports drink (with 200+ calories) to the pool and drink it halfway through the session.

2. If blood glucose level is <180: Eat a small snack before training AND take a bottle of sports drinks to the pool, drinking it halfway through the session.

Connecting the two problems:

It is very unlikely that you will get an HIPO by training on an empty stomach in the morning, unless of course the workout is longer than 1 hour or you woke up with an extremely low blood glucose level. Swimming is the discipline that has a stronger impact on your blood glucose levels if you were to do them all at a similar intensity.?

One way to manage those two problems is by working on the training schedule. This athlete has only access to a pool at lunch time and has a group bike to train with in the morning. But if you can swim in the morning and run/bike at lunch/evening, that would keep your blood glucose levels steadier.

Plus, swimming in the morning is always best for those without a swimming background since you get to train on a fresher body, struggle less to float in the water, therefore getting more quality out of the sessions.

Type 2 diabetes is a disease in which blood sugar levels are above normal and is responsible for over one million amputations each year! If you are diabetic, you may be interested to know how to lower blood sugar level naturally without the use of drugs. Here is a practical quiz that will give you some interesting tips in order to treat diabetes naturally:

1) Should I eliminate all type of carbohydrates from my diet

Some carbohydrates affect blood sugar more than others. Simple carbohydrates such as table sugar (sucrose), honey (fructose), sweet, ice-cream, soda pop, cake and jam make your blood glucose level go up quickly. Avoid these simple carbohydrate foods as much as possible. Sometimes, as a part of a balanced diet, you can eat them in small quantities.

What about complex carbohydrates They are made up of very long chains of glucose molecules and are a much better source of energy for diabetics. For example, most vegetable, beans, brown rice and other whole grains are complex carbohydrates which contain fiber take longer to digest and can help to keep glucose level stable.

2) Should I lose weight

If you are overweight and have type 2 diabetes, losing weight can help you control your blood sugar levels. But before starting a weight loss plan, it is important to keep your doctor inform of any change to your diet.

3) Is it advised to do exercises in order to lower blood sugar quickly

Regardless of their age, diabetic patients can control blood sugar level doing regular aerobic exercise (walking, cycling, swimming, dancing) for at least 30 minutes daily.What are some advantages of doing regular physical activity in Type 2 diabetes

Physical activity stimulates muscle glucose (sugar) uptake, increases insulin sensitivity and promotes weight loss. As the result, it will help to decrease the amount of glucose present in the blood or glycemia. It is important to warm-up properly during 5 to 10 minutes doing the exercises slowly so that you stretch your muscles softly.

4) Can exercise be dangerous for some diabetic patients

If you suffer from diabetes it is better to consult a physician before beginning an exercise program. For diabetic patients who have no other complications, aerobic is safe and beneficial. But in case of other complications, your doctor can determine whether or not you should be exercising.

5) Alcohol consumption can help me to control my diabetes

If you have diabetes, you may drink moderate amount of alcohol but never on an empty stomach! Why Because after consumption of alcoholic beverages on an empty stomach, the liver has to work very hard to metabolize alcohol and has difficulties to regulate blood sugar levels properly. As the result, the use of alcoholic beverages can lead to hypoglycemia.

6) Can vitamins and minerals reduce blood glucose levels

Some clinic studies have found that vitamin D and chromium (mineral) can help to control blood glucose levels. High chromium food sources include liver, eggs, chicken, beef, spinach, whole-grain breads and apple.

7) Can herbs decrease blood sugar levels naturally

There are plenty of herbal remedies able to lower blood sugar levels. For example, bitter melon, stevia, cinnamon, garlic, aloe vera, fenugreek, psyllium, ginseng, gymnema sylvestre, French beans and ginkgo biloba have been found effective for natural treatment of type 2 diabetes mellitus.

Is stress really bad for people with type 2 diabetes

Yes! Stress affects blood glucose levels in someone with diabetes. Actually, stress hormones (cortisol and epinephrine) contribute to elevate blood sugar. Try stress relief relaxation techniques if you are one of the victims of stress.

Are there other effective ways to help control diabetes naturally

Insulin Resistance Warning Signs

If you are heavy set, middle aged, have high blood pressure, low activity levels, feel lethargic all the time, and happen to eat a poor diet, the chances are very good that you have an increased risk for developing heart disease and for potentially developing diabetes. The chances are also good that you already have insulin resistance to a certain degree. This condition is essentially the early warning sign for diabetes and if left unaddressed can become a prelude to a lifetime of health issues.

It is very important to improve insulin resistance if you are experiencing the symptoms. Many people when they go to the doctor and get blood work drawn find that they have normal fasting blood sugar levels and they feel that this means they are fine however poor insulin sensitivity suggests that it takes more insulin to manage blood sugar levels than it should. Ask your doctor if the blood work being done checks for insulin levels in the blood as this is a better indication of whether you have to begin improving insulin resistance or not.

The Importance of Improving Insulin Resistance

If in fact you do show some signs of early resistance of insulin and increased insulin production then you need to understand the gravity of the situation. If you do not begin improving insulin sensitivity in your life you will be walking a fine line between good health and developing diabetes. Yes, it will take time but if not action is taken it will occur. If indeed you do nothing and eventually develop diabetes you will be forced to change your lifestyle as you body will longer be able to produce enough insulin to regulate blood sugar safely.

Diabetes is one of the top causes of death in America and avoiding it at all costs is in your best interests. You do not want to succumb to this disease. You can begin the processes of addressing your insulin issues by simply eating less food and particularly by eating less processed foods and refined carbohydrates. Simultaneously you should begin exercising which is the number one way to improve insulin resistance. In time with a lot of work and a new lifestyle you can be sure to be more healthy and ready for the rest of your life.

Results from a small experimental study suggest that free fatty acids (FFAs) play a role in inducing insulin resistance and may be linked to atherogenic processes regulated by the expression of the cell surface scavenger receptor CD36.

“Abnormalities in lipid metabolism, as observed in obesity and Type 2 diabetes mellitus, result in chronic elevations of plasma FFA levels, which have been reported to contribute to the development of insulin resistance, inflammation, and endothelial dysfunction in diabetic and nondiabetic individuals,” say Sangeeta Kashyap and colleagues from the Cleveland Clinic Foundation in Ohio, USA.

Less is known about the in vivo mechanisms through which increased levels of FFAs promote endothelial dysfunction and atherogenesis, but the cell surface scavenger receptor CD36 is thought to facilitate transport of FFAs into cells.

Kashyap and team investigated the lipid-induced insulin resistance, endothelial dysfunction, and the capacity of monocytes to form foam cells through the action of scavenger receptor A (SRA) and CD36 in 10 healthy volunteers.

The participants underwent a 24-hour infusion of intralipid/heparin plus saline (0.5 ml/min) on two different occasions. This was followed by brachial artery reactivity testing and a euglycemic hyperinsulinemic (80 mU/kg/min) clamp to assess insulin sensitivity.

Blood was also taken 24 hours after the infusion to isolate and study monocytes and their surface expression and functionality (uptake of oxidized low-density lipoprotein [oxLDL]) of SRA and CD36.

Writing in the journal Obesity, the researchers report that the lipid infusion led to a two-fold increase in the level of serum FFAs and a reduction in glucose disposal from the whole body of around 20%. A slight impairment of endothelial-dependent vasodilation was also observed.

There was a mean 25% increase in the cell surface expression of CD36 on the extracted monocytes, but not in that of SRA. This increase in CD36 expression led to a 50% increase in uptake of oxLDL and was inversely correlated with glucose disposal, which is in agreement with previous study results reported by MedWire News.

“All these data taken together suggest that lipid-induced insulin resistance or lipotoxicity is associated with atherogenesis and inflammation associated with scavenger receptor CD36 expression,” conclude Kashyap et al.

They suggest: “Selective downregulation of mononuclear/macrophage CD36 expression and/or inhibition of CD36 function pharmacologically may be an effective therapeutic strategy to retard atherosclerosis accelerated by lipid-induced metabolic diseases.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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CD36 linked to insulin sensitivity and level of IL-6