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The objective of treatment for obesity, type 2 diabetes and hypertension is both to reduce the high risk of cardiovascular events and to prevent or delay the onset of type 2 diabetes and complications. Lifestyle intervention with diet and exercise leading to weight loss prevents and delays the onset of type 2 diabetes or glucose intolerance [ 75 ].

Weight loss may also prevent cardiovascular- and renal-complications [ 76 - 79 ], and renal function and left ventricular hypertrophy as a marker for future cardiac events in obese individuals with metabolic syndrome and hypertension [ 77 , 80 ]. The US Diabetes Prevention Program [ 81 ] and the Oslo Diet and Exercise Study [ 82 ] have shown marked clinical benefits with lifestyle intervention, and modest weight loss, on the resolution of the metabolic syndrome and type 2 diabetes.

A limited number of epidemiological studies have shown that intentional weight loss may be associated with increased mortality and fat loss may reduce the all-cause mortality rate [ 83 ]. Cohort studies with lifestyle intervention [ 84 ] and case control studies with bariatric surgeries [ 85 , 86 ] also provide some evidence that intentional weight loss has long-term benefits on all cause mortality in overweight adults. In a cohort of patients enrolled in a cardiac rehabilitation program, weight loss was associated with favourable long-term outcomes on the composite end-point of mortality and acute cardiovascular events fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, emergent revascularization for unstable angina pectoris, and congestive heart failure [ 87 ].

Many clinical studies have demonstrated that weight loss associated with life-style modification adds to the first line treatment for diabetes mellitus and the efficacy of antihypertensive pharmacological treatments [ 8 ], however, maintaining weight loss is often the greatest challenge [ 5 , 6 , 88 ]. The American Diabetes Association ADA has recommended for the maintenance of a healthy weight to prevent and control diabetes as following; i more than 2. Recently, several investigations [ 4 , 5 , 90 ] compared the effects on weight loss between calorie restriction diet and exercise.

They showed that combined intervention with diet and exercise proved to be effective in weight reduction than diet alone or exercise alone. Masuo et al. There are discordant results on the effects of diet and exercise on weight loss and weight loss-induced blood pressure reductions, however many large cohort interventions and clinical studies have shown combination weight loss regimens with mild calorie restriction and mild exercise was the most effective for significant weight loss compared to diet alone or exercise alone. A low caloric diet and exercise exert different effects on insulin resistance, the RAAS, and sympathetic nervous activity in obese hypertensive subjects, even though similar weight loss was observed [ 4 , 5 ].

Low caloric diet may be prominent for normalization of sympathetic nervous activity and exercise may be related more to normalization of insulin resistance [ 5 , 88 ] Figure 4. They previously observed that baseline plasma norepinephrine levels could predict future weight gain and weight gain-induced blood pressure elevation over 5 years in a longitudinal study [ 91 ], resistant weight loss by weight loss intervention with combination of calorie restriction and exercise intervention over 2 years. Ribeiro et al.

They observed that only exercise, not diet, significantly increased forearm blood flow. When significant chages were observed comparisons between a calorie restricted diet vs. Santarpia et al. At a long term follow up over one year , relatively high protein, moderately low calorie, low glycemic index diets, associated with a daily, moderate intensity, physical exercise of at least 30 min , appear to be more successful in limiting long term rebound, maintaining fat-free-mass and achieving the highest fat loss.

Diet alone or physical exercise alone does not produce similar results. Adequate dietetic advice plus regular physical exercise avoid the fat-free-mass loss usually observed in the rebound of the weight cycling syndrome and prevent the onset of sarcopenic obesity. Exercise training is important for weight loss and to prevent rebound weight gain after significant weight loss.

Public health interventions promoting walking are likely to be the most successful. Indeed, walking is unique because of its safety, accessibility, and popularity. It is noteworthy that there is a clear dissociation between the adaptation of cardiopulmonary fitness and the improvements in the metabolic risk profile such as insulin resistance and sympathetic activation, which can be induced by endurance training programs.

Dumortier et al. It appears that as long as the increase in energy expenditure is sufficient, low-intensity endurance exercise is likely to generate beneficial metabolic effects that would be essentially similar to those produced by high-intensity exercise [ 98 ]. The clinician should therefore focus on the improvement of the metabolic profile rather than on weight loss alone [ 98 ]. Recently, several large cohort studies have shown that saturated fat, which comes mainly from animal sources of food, raises LDL cholesterol and links strongly to cardiovascular risk [ 99 , ].

Saturated fats are needed for the production of hormones, the stabilization of cellular membranes, the padding around organs, and for energy. A deficiency in the consumption of saturated fats can lead to age-related declines in white blood cell function, along with dysfunction of the immune system and cancer [ ]; however, a high content of saturated fat can leads to coronary heart disease [ ], ischemic heart disease, and atherosclerosis and increase the chances of stroke. Consistent evidence from prospective observational studies of habitual trans fatty acids TFA consumption and retrospective observational studies using TFA biomarkers indicates that TFA consumption increases risk of clinical coronary heart disease, and other disease outcomes such as cancer [ ].

Both types of unsaturated fat- mono-unsaturated and poly-unsaturated fats can replace saturated fats in the diet. Substituting saturated fats with unsaturated fats help to lower levels of total cholesterol and LDL cholesterol in the blood. However, intake of unsaturated fats in very high amounts can also increase the risk of coronary heart diseases. Monounsaturated fat: This is a type of fat found in a variety of foods and oils. Studies show that eating foods rich in monounsaturated fats MUFAs improves blood cholesterol levels, which can decrease the risk of heart disease.

Research also shows that MUFAs may benefit insulin levels and blood sugar control, which can be especially helpful for type 2 diabetes. The Swedish Mammography Cohort study including 34, women with a mean follow-up of Similarly, Chowdhury et al. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish. PUFAs decrease the risk of type 2 diabetes. One type of polyunsaturated fat, a long chain omega-3 fatty acids is especially beneficial to coronary heart disease.

Controlled trials and observational studies provide concordant evidence that consumption of TFA from partially hydrogenated oils adversely affects multiple cardiovascular risk factors, and contributes significantly to increased risk of coronary heart disease events. The public health implications of ruminant TFA consumption appear much more limited. Interestingly, incidence of insulin resistance is lowered with diets higher in monounsaturated fats especially oleic acid , while the opposite is true for diets high in polyunsaturated fats especially large amounts of arachidonic acid as well as saturated fats.

It is recommended to take both in a limited quantity. Low-carbohydrate diets are dietary programs that restrict carbohydrate consumption usually for weight control or for the treatment of obesity. Recently, the low carbohydrate diets has been spotlighted due to strong effects on weight loss, but many investigations have also shown no benefits on the reductions on cardiovascular risk as the major aim of weight loss.

In contrast, a low-carbohydrate diet with largely animal sources of protein and fat increases mortality, with a hazard ratio of 1. A meta-analysis that included randomized controlled trials found that "low-carbohydrate, non-energy-restricted diets, appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year [ ].

Gardner et al. Weight loss was significantly greater for women in the Atkins diet group low carbohydrate compared with the other 3 diet groups at 12 months, and weight loss in the other 3 groups were similar, but at 12 months, secondary outcomes for the Atkins group were more favorable metabolic effects than the other diet groups. While questions remain about long-term effects and mechanisms, a low-carbohydrate, high-protein, high-fat diet may be considered a feasible alternative recommendation for weight loss. However, some investigators suggested that that one of the reasons people lose weight on low carbohydrate diet is related to the phenomenon of spontaneous reduction in food intake [ ].

Previously, in routine practice a reduced-carbohydrate, higher protein diet was recommended approach to reducing the risk of cardiovascular disease and type 2 diabetes [ ]. In , the American Diabetes Association ADA affirmed its acceptance of carbohydrate-controlled diets as an effective treatment for short-term up to one year weight loss among obese people suffering from type 2 diabetes [ ]. The recommendation, however, fell short of endorsing low-carbohydrate diets as a long-term health plan nor do they give any preference to these diets.

On the other hand, the official statement from the American Heart Association AHA regarding these diets states categorically that the association doesn't recommend high-protein diets [ 35 ]. A science advisory from the AHA further states the association's belief that these diets are associated with increased risk for coronary heart disease [ , ]. The AHA has been one of the most adamant opponents of low-carbohydrate diets. The American Heart Association supported low-fat and low-saturated-fat diets, but that a low-carbohydrate diet could not potentially meet AHA guidelines.

Recently, the effectiveness of low-fat high- protein and low-fat high-carbohydrate dietary advice on weight loss were compared using group-based interventions, among overweight people with type 2 diabetes. However, in a 'real-world' setting, prescription of an energy-reduced low-fat diet, with either increased protein or carbohydrate, results in similar modest losses in weight, waist circumference and metabolic benefits over 2 years [ ].

Ebbeling et al. Resting energy expenditure REE , total energy expenditure TEE , hormone levels, and metabolic syndrome components at pre-weight-loss were compared. The concept of the glycemic index was developed about by Dr. David Jenkins to account for variances in speed of digestion of carbohydrates. This concept classifies foods according to the rapidity of their effect on blood sugar levels — with fast digesting simple carbohydrates causing a sharper increase and slower digesting complex carbohydrates such as whole grains a slower one.

The concept has been extended to include amount of carbohydrate actually absorbed as well, despite differences in glycemic index [ ]. If the individuals failed to improve glucose levels or HbA1c, pharmacological therapy is required. The first-line oral agents should minimize the degree of insulin resistance and suppress hepatic glucose production rather than increase plasma insulin concentrations. The decision to include thiazolidinediones TZDs and metformin as first-line therapy draws from the algorithm proposed by Wyne et al.

Garber et al. The goal for glucose control is shown in Table 2 [ 11 , ]. Stimulating insulin secretion and minimizing insulin resistance both have the potential to bring a patient to goal, but it is theorized that bringing a patient to goal by reducing insulin resistance is more likely to reduce the macro-vascular complications and cardiovascular risks.

Diabetes Care 26 Suppl. Based on several long-term, prospective studies which showed the significant reductions in cardiovascular risks associated with diabetes, the American Diabetes Association and American Association of Clinical Endocrinologists set forth standards and guidelines for the medical management of diabetes [ 11 ]. The recommendations clearly outline a multifactorial plan for managing diabetes and reducing complications [ 11 ], but they do not provide specific recommendations for selection and titration of pharmacological treatment.

Pharmacological treatment for glucose control aims to reduce cardiovascular risk and to delay diabetic complications. Pharmacological treatment for the management of obesity is primarily aimed at weight loss, weight loss maintenance and cardiovascular risk reduction. Anti-obesity agents decrease appetite, reduce absorption of fat or increase energy expenditure.

Recently, anti-obesity drugs such as orlistat, sibtramine and rimonabant have been developed and placed on markets, however, the latter two were withdrawn from markets in the United States, Europe and Australia due to serious adverse events including psychiatric and cardiovascular related concerns. Recently, contrave, a combination of two approved drugs of bupropion and naltrexone, completed Phase III trials with significant weight loss and was approved by FDA in , but subsequently the FDA declined to approve contrave due to serious cardiovascular adverse events in [ ].

Importantly, obesity is, at least, in part, determined by genetic backgrounds [ ], suggesting that a genetic approach to limiting obesity may find a place in the future. Gastric bypass and adjustable gastric banding are the two most commonly performed bariatric procedures for the treatment of morbid obesity or obesity which is resistant to lifestyle modification such as a low caloric diet plus exercise. Multiple mechanisms contribute to the improved glucose metabolism seen after bariatric surgery, including caloric restriction, changes in the enteroinsular axis, alterations in the adipoinsular axis, release of nutrient-stimulated hormones from endocrine organs, stimulation from the nervous system, and psychosocial aspects including a dramatic improvement in quality of life [ ].

Dixon et al. Koshy et al. The percent of excess weight loss at 4 years was higher in the gastric bypass group compared to the gastric banding group.

Diabetes: The differences between types 1 and 2

Concurrent with restoration of insulin sensitivity and decreases in plasma leptin were dramatic decreases in skeletal muscle at 3 and 9 months after gastric banding and a significant decrease in peroxisome proliferation activated receptor-alpha-regulated genes at 9 months. Gumbs et al. Improvements in glucose metabolism and insulin resistance following bariatric surgery occur, in the short-term from decreased stimulation of the entero-insular axis by restricted calorie intake and in the long-term by decreased release of adipocytokines due to reduced fat mass.

Leptin levels drop and adiponectin levels rise following laparoscopic adjustable gastric banding and gastric bypass. These changes correlate with weight loss and improvement in insulin sensitivity [ ]. All forms of weight loss surgery lead to calorie restriction, weight loss, decrease in fat mass, and improvement in insulin resistance, type 2 diabetes mellitus, obesity and obesity-related hypertension [ ]. Left ventricular relaxation impairment, assessed by tissue Doppler imaging, normalized 9 months after surgery [ ]. Laparoscopic gastric bypass and gastric banding are both safe and effective approaches for the treatment of morbid obesity, but gastric bypass surgery seems to exert a better early weight loss and more rapid ameliorative effects on insulin resistance and adipocytokines, muscle metabolism and left ventricular function.

The prevalence of diabetes, especially type 2 diabetes and hypertension are significantly increased due, at least in part, to the increased prevalence of obesity. Type 2 diabetes is frequently associated with obesity, and is an important risk factor for cardiovascular morbidity and mortality and cardiac- and renal complications. Importantly, these characteristics, themselves, confer cardiovascular risk. Therefore, treatments for type 2 diabetes should be selected from favourable effects on stimulated RAAS, elevated sympathetic nervous system activity, insulin and leptin resistance. Weight loss is recommended as the first line of treatment for type 2 diabetes and hypertension associated with type 2 diabetes in obesity.

Lifestyle modification such as a caloric restricted diet, reducing sedentary behaviour and increases in exercise form the basis of all therapy. Recently, Masuo et al. Exercise had stronger effects on normalizing the RAAS stimulation, sympathetic activation and insulin resistance compared to diet only. The observations demonstrate that a combination therapy for weight loss with a low caloric diet and exercise is recommended for weight loss due to stronger suppression of insulin resistance and sympathetic activation, which both, themselves, are known as risk factors for cardiovascular events.

Although few studies have observed changes in body weight, blood pressure, RAAS, sympathetic nervous activity, insulin resistance and leptin resistance over a long duration such as more than 2 years, Masuo et al. Maintenance of weight loss is another key factor to delay and prevent type 2 diabetes and to reduce cardiovascular risks in type 2 diabetes in obesity. In addition, special diets such as a low carbohydrate diet were reported as beneficial on weight loss previously, but it might cause an increase in cardiac risk.

The official statement from American Heart Association reported that high-protein diet and low carbohydrate diet are not recommended diets due to increases in cardiovascular risk. Weight loss by bariatric surgery leads to improvement or normalization of glucose metabolisms from multiple mechanisms including caloric restriction, changes in the enteroinsular axis, alterations in the adipoinsular axis, release of nutrient-stimulated hormones from endocrine organs, stimulation from the nervous system, and psychosocial aspects including a dramatic improvement in quality of life.

Understanding the mechanisms underlying type 2 diabetes in obesity may help to achieve weight loss and maintenance of weight loss and resultant better control on type 2 diabetes, and delay and prevent the onset of type 2 diabetes or reduce complications. This review provides information regarding, i the importance of lifestyle medication on type 2 diabetes in obesity , ii different effects of lifestyle modifications on weight loss and neurohormonal parameters between diet and exercise, and iii the mode of weight loss and how it influences different physiological pathways.

Different mechanisms may contribute to control in blood glucose levels and blood pressure and cardiovascular risks associated with weight loss with the relevant physiological mechanisms at play being dependent on the mode of weight loss. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.

Help us write another book on this subject and reach those readers. Login to your personal dashboard for more detailed statistics on your publications. Edited by Kazuko Masuo. Edited by Oluwafemi Oguntibeju. We are IntechOpen, the world's leading publisher of Open Access books. Built by scientists, for scientists. Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Introduction The prevalence of diabetes, especially type 2 diabetes and hypertension are significantly increased with the prevalence of obesity Figures 1 , 2 and 3 [ 1 , 2 ].

Type 2 diabetes versus Type 1 diabetes Prevalence of diabetes has increased markedly over the last 20 years in parallel with obesity Figures 2 and 3 [ 1 , 2 ]. Type 1 diabetes Insulin-dependent diabetes Type 1 diabetes is an auto-immune disease targeting on the insulin-producing beta cells in the pancreas. Gestational diabetes mellitus Gestational diabetes, or glucose intolerance, is first diagnosed during pregnancy through an oral glucose tolerance test.

Your body either cannot produce insulin or does not use it properly. Although the projected number of Americans that will have type II diabetes in the year will double from million to million cases Affected age group: Between 5 - 25 maximum numbers in this age group; Type 1 can affect at any age Until recently, the only type of diabetes that was common in children was Type 1 diabetes, most children who have Type 2 diabetes have a family history of diabetes, are overweight, and are not very physically active.

Table 1. Comparison between type 1 diabetes and type 2 diabetes. Prevalence of type 2 diabetes The prevalence of type 2 diabetes has dramatically increased in parallel in rising prevalence of obesity Figures 1 and 2 , and it increases with obesity Figure 3. What causes type 2 diabetes? Lifestyle A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity, lack of physical activity sedentary life style [ 12 ], poor diet, stress, and urbanization.

Genetics Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic. Medical conditions There are a number of medications, including glucocorticoids, thiazides, beta blockers, atypical antipsychotics, and statins that can predispose to diabetes [ 25 ]. Type 2 diabetes mellitus as a risk factor for cardiovascular disease Several epidemiological studies are available to understand that diabetes is a strong cardiovascular disease risks.

Neurohoromonal characteristics in type 2 diabetes: Insulin resistance and sympathetic activity It is widely recognized that insulin resistance is a major mechanism of the onset of type 2 diabetes.

Diabetes mellitus (type 1, type 2) & diabetic ketoacidosis (DKA)

Treatments for type 2 diabetes Weight loss is recommended as the first line of treatment for type 2 diabetes and hypertension associated with obesity, because obesity is the primary cause for insulin resistance, metabolic syndrome and type 2 diabetes. Lifestyle modification for weight loss Weight loss is recommended as the first-line treatment for obesity-related type 2 diabetes and hypertension.

Calorie restricted diet versus aerobic exercise The American Diabetes Association ADA has recommended for the maintenance of a healthy weight to prevent and control diabetes as following; i more than 2. Dietary 7. Saturated fat versus unsaturated fat Recently, several large cohort studies have shown that saturated fat, which comes mainly from animal sources of food, raises LDL cholesterol and links strongly to cardiovascular risk [ 99 , ].

Special diet Low Carbohydrate Diet Low-carbohydrate diets are dietary programs that restrict carbohydrate consumption usually for weight control or for the treatment of obesity. Low fat diet Recently, the effectiveness of low-fat high- protein and low-fat high-carbohydrate dietary advice on weight loss were compared using group-based interventions, among overweight people with type 2 diabetes.

Low glycemic index The concept of the glycemic index was developed about by Dr. Pharmacological treatments for type 2 diabetes If the individuals failed to improve glucose levels or HbA1c, pharmacological therapy is required. Table 2. Bariatric surgery Gastric bypass and adjustable gastric banding are the two most commonly performed bariatric procedures for the treatment of morbid obesity or obesity which is resistant to lifestyle modification such as a low caloric diet plus exercise. Conclusion The prevalence of diabetes, especially type 2 diabetes and hypertension are significantly increased due, at least in part, to the increased prevalence of obesity.

More Print chapter. How to cite and reference Link to this chapter Copy to clipboard. However, whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk is not known [ ]. The proposed mechanisms of metformin anti-cancer properties are not fully understood. Some of these mechanisms may be through inhibition of cell growth [ ], IGF-1 signaling [ ], inhibition of the mTOR pathway [ ], reduction of human epidermal growth factor receptor type 2 HER-2 expression a major driver of proliferation in breast cancer [ ], inhibition of angiogenesis and inflammation [ ], induction of apoptosis and protein 53 p53 activation [ ], cell cycle arrest [ , ], and enhancement of cluster of differenciation 8 CD8 T cell memory [ ].

In vitro and in vivo studies strongly suggest that metformin may be a valuable adjuvant in cancer treatment. Some of the proposed future roles yet to be defined through further research are outlined as follows:. When compared to those on other treatments, metformin users had a lower risk of cancer. A dose-relationship has been reported [ , , ]. Type 2 diabetic patients receiving neo-adjuvant chemotherapy for breast cancer as well as metformin were more likely to have pathologic complete response pCR than patients not receiving it. However, despite the increase in pCR, metformin did not significantly improve the estimated 3-year relapse-free survival rate [ ].

Cancer stem cells may be resistant to chemotherapeutic drugs, therefore regenerating the various tumor cell types and promoting disease relapse. Low doses of metformin inhibited cellular transformation and selectively killed cancer stem cells in four genetically different types of breast cancer in a mouse xenograft model. The association of metformin and doxorubicin killed both cancer stem cells and non-stem cancer cells in culture. This may reduce tumor mass and prevent relapse more effectively than either drug used as monotherapy [ ]. Metformin is contraindicated in patients with diabetic ketoacidosis or diabetic precoma, renal failure or renal dysfunction, and acute conditions which have the potential for altering renal function such as: dehydration, severe infection, shock or intravascular administration of iodinated contrast agents, acute or chronic disease which may cause tissue hypoxia cardiac or respiratory failure, recent myocardial infarction or shock , hepatic insufficiency, and acute alcohol intoxication in the case of alcoholism and in lactating women [ ].

Several reports in literature related an increased risk of lactic acidosis with biguanides, mostly phenformin, with an event rate of 40—64 per , patients years [ ] whereas the reported incidence with metformin is 6. Structural and pharmacokinetic differences in metformin such as poor adherence to the mitochondrial membrane, lack of interference with lactate turnover, unchanged excretion, and inhibition of electron transport and glucose oxidation may account for such differences [ ].

Despite the use of metformin in cases where it is contraindicated, the incidence of lactic acidosis has not increased. Most patients with case reports relating metformin to lactic acidosis had at least one or more predisposing conditions for lactic acidosis [ ]. Renal dysfunction is the most common risk factor associated with lactic acidosis but so far there is no clear evidence indicating at which level of renal dysfunction metformin should be discontinued or contraindicated in order to prevent lactic acidosis. Some authors have suggested discontinuing its use when serum creatinine is above 1.

As serum creatinine can underestimate renal dysfunction, particularly in elderly patients and women, the use of estimated GFR eGFR has been advocated. The dose of metformin should be reviewed and reduced e. Metformin should not be initiated in patients at this eGFR [ ]. Frid et al. Another clinical condition associated with lactic acidosis in patients using metformin is heart failure [ 79 ]. Gastrointestinal intolerance occurs quite frequently in the form of abdominal pain, flatulence, and diarrhea [ ].

Most of these effects are transient and subside once the dose is reduced or when administered with meals. This vitamin B12 deficiency is rarely associated with megaloblastic anemia [ ]. Other adverse reactions are sporadic, such as leucocytoclastic vasculitis, allergic pneumonitis [ ], cholestatic jaundice [ ], and hemolytic anaemia [ ].

Hypoglycemia is very uncommon with metformin monotherapy [ ] but has been reported in combination regimens [ ], likely due to metformin potentiating other therapeutic agents. Clinically significant drug interactions involving metformin are rare. Some cationic agents such as amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin that are eliminated by renal tubular secretion may compete with metformin for elimination.

Concomitant administration of cimetidine, furosemide, or nifedipine may also increase the concentration of metformin. Patients receiving metformin in association with these agents should be monitored for potential toxicity. Gastrointestinal side-effects are common with the use of metformin of standard release and are usually associated with rapid titration and high-dose initiation of metformin. These effects are generally transient, arise early in the course of treatment, and tend to subside over time [ ]. The gastrointestinal side-effects can be addressed by taking the agent with meals, reducing the rate of dose escalation, or transferring to a prolonged-release formulation [ ].

Some studies point to a dose-related relationship of the incidence of side-effects [ ] whereas other evidence gives no support for a dose-related effect of metformin on the gastrointestinal system [ ]. The metformin XR formulation releases the active drug through hydrated polymers which expand after uptake of fluid, prolonging gastric residence time which leads to slower drug absorption in the upper gastrointestinal tract and allows once-daily administration [ ].

A prospective open label study assessed metformin XR effectiveness on three cardiovascular risk factors: blood glucose HbA1c, fasting blood glucose, and postprandial blood glucose ; total cholesterol, LDL cholesterol, HDL cholesterol; and triglycerides and blood pressure. No significant differences were observed by any anthropometric, clinical, or laboratory measures except for plasma triglycerides which were lower in the group switched to metformin XR [ ].

Metformin tolerability as well as patient acceptance was greater in the group switched to metformin XR. Other studies have found good to excellent glycemic control with metformin XR in type 2 diabetic patients who did not have well-controlled diet and exercise alone [ ]. Metformin XR has been associated with improved tolerability [ ] and increased compliance [ ]. In recent years, metformin has become the first-line therapy for patients with type 2 diabetes.

Thus far, metformin is the only antidiabetic agent which has shown reduced macrovascular outcomes which is likely explained by its effects beyond glycemic control. It has also been employed as an adjunct to lifestyle modifications in pre-diabetes and insulin-resistant states. A large amount of evidence in literature supports its use even in cases where it would be contra-indicated mainly due to the fear of lactic acidosis which has been over-emphasized as the available data suggest that lactate levels and risk of lactic acidosis do not differ appreciably in patients taking this drug versus other glucose-lowering agents.

Godarzi MO, Brier-Ash M: Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents. Diabetes Obes Metab. J Biol Chem. Estimates for the year and projections for Diabetes Care.

Preventing Type 2 Diabetes

Petersen J, Mc Guire D: Impaired glucose tolerance and impaired fasting glucose — a review of diagnosis, clinical implications and management. Diabetes Vasc Dis Res. Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. Diabetes Prevention Program Research Group: Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program.

Chin J Endocrinol Metab. Diab Res Clin Pract.

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Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention

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Donahue S, Marathe P, Guld T, Meeker J: The phamacokinetics and pharmacodynamics of extended-release metformin tablets vs immediate-release metformin in subjects with type 2 diabetes. Diabetol Metab Syndr. Raz I, Delaet I, Goyvaerts H: Safety and efficacy of novel extended-release formulation of metformin in patients with type 2 diabetes. Download references. Both authors read and approved the final manuscript. This article is published under license to BioMed Central Ltd. Reprints and Permissions. Search all BMC articles Search.

Abstract The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. Introduction The discovery of metformin began with the synthesis of galegine-like compounds derived from Gallega officinalis , a plant traditionally employed in Europe as a drug for diabetes treatment for centuries [ 1 ]. Metformin and pre-diabetes In , an estimated million people in the world had diabetes, and the numbers are projected to double by Table 1 Effectiveness of metformin in diabetes prevention of patients with impaired glucose tolerance Full size table.

Table 2 Metformin effects on vasculoprotection Full size table. Table 3 Reduced incidence and cancer-related mortality in metformin treated patients Full size table. Conclusions In recent years, metformin has become the first-line therapy for patients with type 2 diabetes. References 1. PubMed Article Google Scholar 5. Article Google Scholar 6.