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Curr Diabetes Rev [journal]
- Targeting Peroxisome Proliferator-Activated Receptor Gamma for Generation of Antidiabetic Drug. [JOURNAL ARTICLE]
- Curr Diabetes Rev 2013 Jun 7.
The incidence of Diabetes Mellitus (DM) has increased to alarming levels not only in developed countries but also in developing and underdeveloped countries. Scientific data have made it clear by now that patients with DM are predisposed to many other diseases. One of the worst associations of DM is with obesity and the number of DM patients with obesity is increasing at a very fast pace due to dramatic change in life style around the world in last few decades. This necessitates the discovery of new drugs to treat increasing numbers of people with both DM and obesity. Peroxisome Proliferator activated receptor gamma (PPARγ) is a well known target for DM and thiazolidiniones (TZDs; a common class of antidiabetic drug) which includes rosiglitazone and pioglitazone act through PPARγ. Recent studies have demonstrated that PPARγ apart from being important in glucose utilization also plays a critical role in lipid metabolism and energy homeostasis affecting long-term metabolic status. The possibility of selective modulation of PPARγ has opened up a whole new avenue of research and has the potential of producing some drug which can simultaneously fight both DM and obesity, without the side-effects of the currently available PPARγ modulators. Here, we discuss various aspects of selective modulation of PPARγ action.
- Time Trends and Gender Differences in Incidence and Prevalence of Type 1 Diabetes In Sweden. [JOURNAL ARTICLE]
- Curr Diabetes Rev 2013 May 31.
There are different opinions on a possible sex bias in diabetes. In Sweden we have access to data since the 1930s, making it an ideal model. We aimed to study gender differences and time trends in the incidence and prevalence of type 1 diabetes in Sweden. We found 30 articles on incidence and 8 on prevalence (6 overlapping). Times series on incidence were found regarding children 0–15 years of age (with the Swedish Childhood Diabetes Registry, SCDR, since 1977), with up to 14,721 children with diabetes and with a high degree of ascertainment. Incidence time series were also found for subjects aged 15–34 (Diabetes Incidence Study in Sweden, DISS, since 1983), with up to 7,369 subjects and with a lower degree of ascertainment compared to SCDR. Regarding age from 40 years and above fewer studies were found, and with a much lower number of subjects with type 1 diabetes. Diabetes incidence in children has had a relative increase of approximately 2% per year since 1938. Incidence rates in children 0–14 years of age show no gender differences, but in subjects aged 15–39 years a male preponderance up to twofold is found. Figures for subjects 40 years or older are more uncertain, but show a fairly equal incidence among men and women. The male preponderance in type 1 diabetes from age 15 up to 40–50 could be due to hormonal influence, with higher peripheral insulin resistance among men in young adults and younger middle age.
- Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus: An Update on Recent Developments. [JOURNAL ARTICLE]
- Curr Diabetes Rev 2013 May 31.
Type 1 diabetes mellitus is an autoimmune disease that is characterized by the destruction of the islets of Langerhans cells which produce insulin. The current gold standard treatment is exogenous insulin injection, but this is onerous for the patients, and can lead to severe complications. Another approach involves transplanting pancreatic islet cells in order to restore endogenous insulin production under physiologic regulation. Although there has been some success with this treatment plan, there have been several hurdles. The largest hurdle is improving the 5 year survival of the graft, which is currently at 10%. In order to do so, there has been research into better locations for the graft, better isolation techniques, alternate immune suppression regimens, and novel transplantation methodologies utilizing encapsulated grafts. Another hurdle for pancreatic islet transplantation is that current methodologies require islets from several pancreata in order to create one successful graft, which leads to difficulties since there is a limited supply. However, there has been research looking into single donor transplants and porcine xenografts to increase the supply and address this problem. In this article, we review the current state of research regarding pancreatic islet transplantation.
- Iron Overload and Glucose Metabolism in Subjects With β-Thalassaemia Major : An Overview. [JOURNAL ARTICLE]
- Curr Diabetes Rev 2013 May 15.
Thalassaemia is one of the most common genetic disorders caused by a reduction of the globin chains leading to chronic haemolytic anaemia from birth. The mainstay of treatment is blood transfusion to maintain adequate levels of the haemoglobin. Iron overload in β-thalassaemia major patients is secondary to multiple blood transfusions and increased iron absorption. Excess iron potentially catalyzes free-radicals generation and impairment in cellular function and integrity. Extensive iron-induced injury develops in the heart, liver, pancreas and endocrine system. Pancreatic iron loading in thalassaemia major patients begins at early childhood, and the prevalence of diabetes mellitus (DM) ranges from 6.4% to 14.1% in cross-sectional studies. Both insulin resistance and decreased insulin secretion contribute to DM in thalassaemia major patients. This has been shown by oral glucose tolerance test, euglycemic insulin clamp, homeostatic model assessment, intravenous glucose tolerance test and continuous glucose monitoring system. The prevalence of DM in thalassaemia has been shown to correlate with serum ferritin concentration, hepatitis C infection, and pancreatic and cardiac iron measured by imaging techniques. Therefore the incidence of disturbed glucose homeostasis depends on adherence to chelation treatment, the adequacy of the dosage, the chemical properties of the chelating agent and the prevention of liver infections.
- An Overview Of Valuable Scientific Models For Diabetes Mellitus. [JOURNAL ARTICLE]
- Curr Diabetes Rev 2013 Apr 17.
Diabetes mellitus is one of the major clinical problems worldwide. Previously, most of the investigational studies for identification of disease and new therapies were based on animal studies; however, present research methods involve high throughput screening, molecular targeting, nanotechnology for recent discovery of drugs and disease identification to combat against hazardous diseases like diabetes mellitus. In this review, we have depicted an outlines enfolding various disease-specific animal modeling, sensing technologies, biomarker analysis, and novel scientific techniques that could be helpful in exploring the impending strategies for diabetes detection and treatment. To conclude, we believe that endorsement and upgrading of such novel high throughput screening assays and nanotechnology described herein may surely represent a significant improvement in the capability for screening and identifying the population at elevated risk of expected diabetes. Thereby in future, appreciation of such investigational techniques and technologies including metabolomics and genetic screening may help in early prediction of diabetes in patients at risk and may display a significant improvement over the researchers conducted after the declaration of the disease.
- Association between Seizures and Diabetes Mellitus: A Comprehensive Review of Literature. [JOURNAL ARTICLE]
- Curr Diabetes Rev 2013 Apr 16.
Epilepsy or seizures are often observed in patients with diabetes mellitus (DM), and an emerging association between the two diseases is more than coincidental based on recent research. Approximately 25% of patients with DM experience different types of seizures. Furthermore, diabetic patients who experienced episodes of DKA also have seizures more frequently. The precise pathogenesis of seizures in the diabetes patient remains undetermined. Currently, the leading hypotheses in the literature suggest that multiple physiological factors, such as immune abnormalities, microvascular lesions in the brain, local brain damage, metabolic factors and gene mutation, may contribute to this condition. To date, there are no international criteria for the diagnosis and treatment of this condition. Although it is commonly assumed that antiepileptic drugs are necessary, most of the partial epilepsy patients with non-ketotic diabetes are resistant to frequently used antiepileptic drugs. In contrast, partial status epilepticus can be treated by diazepam, and carbamazepine is reported to be effective to some DM patients with epilepsy. However, anti-diabetic drugs are considered to be the most important factors in the treatment of this condition. When the blood glucose levels gradually return to normal levels, patients can no longer generate seizures even when antiepileptic drugs are discontinued.
- A Systematic Review of Overweight, Obesity, and Type 2 Diabetes Among Asian American Subgroups. [JOURNAL ARTICLE]
- Curr Diabetes Rev 2013 Apr 11.
This systematic review synthesizes data published between 1988 and 2009 on mean BMI and prevalence of overweight, obesity, and type 2 diabetes among Asian subgroups in the U.S. We conducted systematic searches in PubMed for peer-reviewed, English-language citations that reported mean BMI and percent overweight, obesity, and diabetes among South Asians/Asian Indians, Chinese, Filipinos, Koreans, and Vietnamese. We identified 647 database citations and 23 additional citations from hand-searching. After screening titles, abstracts, and full-text publications, 97 citations remained. None were published between 1988 and 1992, 28 between 1993 and 2003, and 69 between 2004 and 2009. Publications were identified for the following Asian subgroups: South Asian (n=8), Asian Indian (n=20), Chinese (n=44), Filipino (n=22), Korean (n= 8), and Vietnamese (n=3). The observed sample sizes ranged from 32 to 4245 subjects with mean ages from 24 to 78 years. Among samples of men and women, the lowest reported mean BMI was in South Asians (22.1 kg/m2), and the highest was in Filipinos (26.8 kg/m2). Estimates for overweight (12.8 - 46.7%) and obesity (2.1 - 59.0%) were variable. Among men and women, the highest rate of diabetes was reported in Asian Indians with BMI ≥ 30 kg/m2 (32.9%, age and sex standardized). This review suggests heterogeneity among U.S. Asian populations in cardiometabolic risk factors, yet comparisons are limited due to variability in study populations, methods, and definitions used in published reports. Future efforts should adopt standardized methods to understand overweight, obesity and diabetes in this growing U.S. ethnic population.
- Role of sulfur containing amino acids as an adjuvant therapy in the prevention of diabetes and its associated complications. [Journal Article]
- Curr Diabetes Rev 2013 May; 9(3):237-48.
Amino acid supplementation is gaining acceptance as an important adjuvant therapy in the treatment of diabetes and its associated complications. Numerous studies in the literature report the impaired amino acid metabolism in diabetes and the beneficial effects of amino acids are positively correlated with the increase in plasma levels of those amino acids. Oxidative stress is known to play a major role in diabetic pathophysiology. Sulfur containing compounds are well known in the treatment of oxidative stress induced pathological disorders. Methionine, cysteine, and homocysteine are the three common sulfur containing amino acids. In addition, taurine, a sulfonic acid containing an amino group (amino sulfonic acid), is found in substantial amounts in mammalian tissues. Both experimental and clinical studies reported the modulatory effects of cysteine, N-acetyl cysteine, or compounds having cysteine moiety in the regulation of insulin secretion and plasma glucose levels. Taurine supplementation has been found to prevent the onset of diabetes mellitus in experimental models of both insulin dependent and insulin independent pathways. Recent reports suggest that the beneficial role of cysteine or taurine is mediated via their ability in reducing glycooxidation and preventing the generation of intracellular reactive intermediates. Studies with methionine or S-adinosyl methionine has been shown to increase mitochondrial DNA density in skeletal muscle, improve insulin sensitivity and prevent body weight gain. Homocysteine, on the other hand, is an emerging risk factor for cardiovascular disease and diabetic patients have higher levels of this sulfur containing amino acid. Supplementation with cysteine or taurine, however, was found to be effective in reducing plasma homocysteine levels. This review will discuss the role of sulfur containing amino acids in the regulation of hyperglycemia and in the development of its associated pathological dysfunctions.
- Modulation of P2 receptors on pancreatic β-cells by agonists and antagonists: a molecular target for type 2 diabetes treatment. [Journal Article]
- Curr Diabetes Rev 2013 May; 9(3):228-36.
Morbidity and mortality from diabetes mellitus (DM) are serious worldwide concerns. By the year 2030, the estimated number of diabetic patients will reach a staggering 439 million worldwide. Diabetes mellitus type 2 (DM2), which involves disturbances in both insulin secretion and resistance, is the most common form of diabetes and affects approximately 5 to 7% of the world's population. When a patient with DM2 cannot regulate his or her blood glucose levels through diet, weight loss, or exercise, oral medications, such as hypoglycemic agents (i.e., sulphonylureas, biguanides, alpha glucosidase inhibitors and thiazolidinediones), are crucial. Here, we discuss some physiological aspects of P2 receptors on pancreatic β-cells, which express a variety of P2 receptor isoforms. These receptors enhance glucose-dependent insulin release. In addition, we speculate on the potential of purinergic compounds as novel or additional treatments for Type 2 Diabetes mellitus.
- Insulin neuritis and diabetic cachectic neuropathy: a review. [Journal Article]
- Curr Diabetes Rev 2013 May; 9(3):267-74.
Diabetic patients can be affected by a wide range of peripheral nerve disorders, the rarer of which are often poorly recognised and understood. "Insulin neuritis" or "treatment induced neuropathy" is a reversible disorder characterised by acute severe distal limb pain, peripheral nerve fibre damage and autonomic dysfunction, preceded by a period of rapid glycaemic control. The condition has been reported in both type 1 and type 2 diabetics treated with insulin or oral hypoglycaemic agents who typically have a history of poor glycaemic control. Pathogenesis of the condition and its associated pain is poorly understood, with proposed mechanisms including endoneurial ischaemia, hypoglycaemic microvascular neuronal damage and regenerating nerve firing. Pain can affect other areas including the trunk and abdomen, or be more generalised. "Diabetic neuropathic cachexia" is a rare disorder associated with poor diabetic control that presents with large amounts of unintentional weight loss associated with an acute symmetrical painful peripheral neuropathy without weakness. Pain is characteristically burning in nature with predominant lower limb involvement and allodynia. The disorder can also affect type 1 and type 2 diabetics and occur irrespective of the duration of their diabetes. Depression and in males, impotence, appear to be common, although other autonomic features can be present. Typically it has a monophasic course but has been reported to be recurrent. As with insulin neuritis, this condition is reversible over weeks to months after adequate diabetic control. For both disorders, the pain can be treatment resistant despite the use of multiple analgesics.