Current Diabetes Reviews - Volume 10, Issue 3, 2014

Diabetes mellitus (DM) represents one of the greatest threats to human health all over the world. The incidence of DM is rising rapidly also including children and young persons of reproductive age. Diabetes has been associated with reproductive impairment in both men and women. Diabetes may affect male reproductive functions at multiple levels as a result of its effects on the endocrine control of spermatogenesis, steroidogenesis, sperm maturation, impairment of penile erection and ejaculation. A large number of studies both on diabetic men and experimental diabetic animals have been published on the impact of DM on male reproductive functions during the past few years but many of them have conflicting results. The present review summarizes the research finding of a large number of research papers on the reproductive functions especially on hypothalmo-pituitary-gonadal axis, spermatogenesis, histopathology of testis, synthesis and secretion of testosterone, sperm quality, ejaculatory function and fertility both in diabetic men and experimental diabetic animals.

Diabetes mellitus (T2DM) has become a global problem. Role of n-3 FA in its prevention is still not completely understood. We carried out this systematic review and meta-analysis to assess the relation of dietary intake of fish and n-3PUFA with risk of diabetes. We searched PUBMED, EMBASE and GOOGLE with cross references to identify relevant articles. Since no RCTs were available, we searched for prospective cohort studies. Sixteen studies with 6,79,763 participants which assessed the association of dietary intake of fish and n-3 PUFA (marine or alpha-linolenic acid) with incidence of T2DM in > 18 years population and provided relative risk (RR) or hazard ratio (HR) with the corresponding 95% confidence interval (CI) of T2DM for each category of fish or n-3 PUFA intake were included. Three independent reviewers reviewed all eligible studies and abstracted the relevant information from individual studies. Meta-analysis confirmed the previous finding that marine n-3 FA increased risk of T2DM in Americans but reduced the same in Asians. We observed that two and seven times increased intake of ALA and fatty fish respectively reduced the risk of T2DM significantly and ALA did not increase the risk in Americans. We concluded that ALA may have some role in preventing T2DM, but is not studied widely. Hence, it should be studied in greater details (with higher degrees of intake; more than two times) to aid in developing effective preventive strategies against diabetes.

Diabetes mellitus is a disease with a devastating impact on population. Recent data revealed that early retinal neuropathy in patients with diabetic retinopathy involved a reduced expression of brain-derived neurotrophic factor. Retinal ganglion cells (RGC) neuropathy is a progressive optic nerve neuropathy with RGC death and axonal degeneration, and it leads to blindness in the elderly population worldwide. Thus, neuroprotective therapies that rescue damaged RGCs and inhibit the progression of RGC loss and axonal degeneration are needed. This review introduces potential neuroprotective therapies using different neurotrophic factors for damaged RGC in eyes with RGC neuropathy associated diseases.

Infections within diabetic foot ulcers are often hard to detect and extremely difficult to treat. The normal signs and symptoms of infection including purulence, erythema, pain, tenderness, warmth and induration are frequently absent in such wounds necessitating exploration of other ways of rapidly and accurately detecting infection. This study considers diabetic wound fluid pH as a possible alternative means of monitoring infection status. CINAHL, Ovid SP and MEDLINE were searched for papers in English published between January 2004 to May 2014. Key search terms included wound fluid, exudate, wound, ulcer, diabetes, pH, healing, infection, bacteria. This paper considers the potential benefits of augmenting and supporting current clinical practice in the early determination of wound healing trajectory and infection status, by monitoring wound fluid pH. The evidence collected highlights the need for further research and suggests the potential of wound fluid analysis as a possible surrogate marker for detecting infection in diabetic foot ulcers.

Nephropathy is one of the major complications of diabetes which further directs to end stage renal disease. Extensive work has been done to find out the mechanisms involved in pathogenesis of the DN. Now, many researchers have been convinced that almost all of the molecular mediators and intracellular signaling pathways involved in progression of diabetic nephropathy have involvement in transforming growth factor beta (TGF- β) at some stage. In DN, hyperglycemia causes increase in the expression of TGF- β genes, TGF- β proteins and their receptors. Increased glucose level mediates these effects through activation of polyol pathway, protein kinase C pathway, hexosamine pathway, increases advanced glycation end products (AGE) and increases oxidative stress. Hyperglycemia also activates the TGF- β via activation of glucose transporters (GLUT), angiotensine II and platelet derived growth factor (PDGF). Activated TGF-β further leads to glomerular basement membrane (GBM) thickening and glomerulosclerosis through activation of connective tissue growth factor (CDGF) and vascular endothelial growth factor (VEGF). We have discussed the progression of hyperglycemia to DN via TGF- β, whose schematic presentation may serve as an effective way to understand the mechanisms and to find out an effective way for the management of diabetic nephropathy.

Obesity and Type 2 diabetes are leading health problems which are characterized by low-grade inflammation with an increase in inflammatory cytokines along with the change in the gut microbiota population. Toll like Receptors (TLRs) and NOD like Receptors (NLRs) are very prominent pathogen recognition receptors, which play a significant role in the innate immune system. Both TLRs and NLRs pathways are mediated through different adaptor proteins; commonly found to activate the NF-kB, which induces the expression of proinflammatory cytokines. It has been suggested that TLRs and NLRs have a significant role in the pathogenesis of inflammation mediated insulin resistance, which further develops metabolic complications. TLRs mediated mechanism for insulin resistance involves activation through TLR ligands such as increased free fatty acids and lipid derivatives from adipocytes as well as the skeletal muscles. Moreover, gut microbiota alteration in the type 2 diabetes also plays a key role by increasing the plasma LPS levels, which specifically activates TLR4 and provokes the inflammation mediated insulin resistance. NOD1 and NOD2 are involved in the pathogenesis of diabetes, possibly through the recognition of the gut microbiota. Gut microbiota modulation by antibiotics plays a crucial role in increasing insulin sensitivity, possibly through the TLRs and NLRs mediated signaling responses, which suggest future therapeutic approaches for obesity, insulin resistance and type 2 diabetes. In this review, we focused on the interdependent role of TLRs and NLRs in metabolic diseases and their cross talk for the pathogenesis of inflammatory diseases.

Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Vascular endothelial dysfunction is an early pathophysiological precursor of cardiovascular disease. There is extensive evidence that hyperglycemia causes acute perturbations in endothelial function likely due to increases in oxidative damage. Interestingly, oscillating hyperglycemia may cause more damage than persistent hyperglycemia. Many, but not all, studies indicate that vascular endothelial dysfunction occurs early in the course of type 1 diabetes and is present even in adolescents. Ascorbic acid has been shown to diminish the acute effects of hyperglycemia on endothelial function in type 1 diabetes and in conjunction with euglycemia to restore endothelial function to normal values in adults with well-controlled diabetes. In vitro and in vivo animal evidence suggests potential benefit from two other small molecule antioxidants, nicotinamide and taurine. Early studies suggested that folate supplementation may improve endothelial function in adolescents with type 1 diabetes but this has not been confirmed by more recent studies. Epidemiological evidence suggests a possible role for vitamin D therapy although intervention studies in type 2 diabetes have yielded varying results and have not been done in type 1 diabetes. Further exploration of these and other compounds is clearly appropriate if we are to reduce cardiovascular risk in type 1 diabetes.

Laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (SG) are the three most commonly performed bariatric procedures. Obesity responds well to bariatric surgery, with major long-lasting weight loss that is most pronounced after RYGB and SG, where the mean weight loss is about 40 kg or 15 body mass index (BMI) units. Some of the benefits after RYGB and SG are independent of weight loss, and the remission of type 2 diabetes is observed a few days after the operation; this depends on changes in insulin sensitivity and gut hormone responses, especially a 10-fold increase in glucagon-like peptide-1 (GLP-1), which improves insulin secretion. After gastric banding, the remission of diabetes depends more on weight loss. Bariatric surgery reduces cardiovascular risk factors including hypertension, lipid disturbances, non-alcoholic fatty liver, musculoskeletal pain and reduces mortality of diabetes, cardiovascular diseases and cancers. Bariatric surgery also improves quality of life. The acute complications of surgery are infection, bleeding and anastomotic leak. Long-term complications are nutritional deficiencies, including vitamins and minerals, and anemia. Some patients have dumping after meals, and a few patients will develop postprandial hypoglycemia after RYGB. About 25% of patients require plastic surgery to provide relief from excessive skin tissue.