Current Diabetes Reviews - Volume 11, Issue 2, 2015

Hepatic cancer stands as one of the frontier causes of cancer related mortality worldwide. Among the several risk factors already established, type 2 diabetes is now considered as one of the important risks in progression of liver cancer. Studies have shown that likelihood of occurrence of liver cancer is many folds higher in patients diagnosed with type II diabetes compared to patients without diabetes. Liver plays an important role in metabolism of glucose in our body, so may be type II diabetes as it is an important epiphenomenon of hepatic diseases such as liver cirrhosis, liver failure, fatty liver, chronic hepatitis and hepatocellular carcinoma. Some reports suggested that extensive change in enzyme structures in molecular level in diabetic patients may lead to liver function damage and hence accelerate hepatic cancer. Other strong links between these two diseases are “non alcoholic fatty liver diseases” and “nonalcoholic steatohepatitis” which are metabolic disorders caused by type II diabetes and eventually develops hepatocellular carcinoma. However, it still remains unanswered whether prevention of diabetes would effectively lower the chances of developing liver cancer or eliminating diabetes from the population would effectively reduce the liver cancer incidence. In this review, we will primarily focus on the molecular link between type2 diabetes and hepatic cancer and investigate underlying mechanism to establish type II diabetes as predisposed cause of hepatic cancer.

Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is a first-line option for the management of MDD and, as a result, the use of antidepressants has increased 4 fold in the last 20 years. Serotonin is the most commonly dysregulated neurotransmitter in the etiology of MDD and this system is the primary focus of most medications used in the treatment of illness. Although antidepressant use in adults increases the risk of developing new onset type 2 diabetes, the mechanisms underlying this association are poorly defined. This review will focus on 1) the evidence from human and animal studies suggesting a link between the use of antidepressants that target serotonin signaling (i.e., SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs)) and increased risk of diabetes, and 2) the mechanisms by which alterations in serotonin signalling by antidepressants can affect glucose homeostasis.

Diabetic macular edema (DME) is the leading cause of moderate vision loss in diabetics. Modalities to image and monitor DME have evolved much in the last decade. Systemic control is the most important part of management. Available ocular management options include intravitreal antivascular endothelial growth factor (anti-VEGF) agents, laser, steroids (intravitreal or peribulbar), vitrectomy, topical medications and others. Anti-VEGF agents are increasingly being used in clinical practice with good clinical response and are currently the preferred mode of treatment worldwide.

The association between diabetes mellitus and coronary artery disease (CAD) is wellknown. Being the leading cause of death in diabetics, CAD is a target for prevention, diagnosis and treatment. In that sense, silent CAD in diabetics has long been a matter of concern, leading both to continued attempts at its diagnosis as well as to the persisting challenge of defining if screening for CAD in the diabetic population is useful and/or warranted. The most frequent and stronger point in favor of screening rests on the assumption that early diagnosis of CAD may lead to early treatment and therefore improved outcomes. Nonetheless, screening for CAD in diabetics is a controversial issue, since studies have not yielded evidence supporting better outcomes in diabetics screened for CAD compared to nonscreened diabetics. For several reasons, current tests that detect inducible ischemia or assess atherosclerotic burden may not be able to identify those patients at increased risk. Therefore a cautious look should be taken (once more) at that question.

Prevalence of diabetes mellitus (DM) is progressively increasing, contributing to a parallel increase in cardiovascular morbidity and mortality, and more than doubling the incidence of sudden cardiac death (SCD). Certain electrocardiographic (ECG) characteristics, such as alternans of the T wave (TWA), heart rate variability (HRV) and dispersion of the QT interval, have been found to be predictive of the risk of SCD. This review focuses on ECG changes that could be found in diabetics and their potential implication for SCD risk.

Excessive dietary intake of fat is strongly involved in the development of type 2 diabetes (T2D). Free fatty acids (FFAs), which are provided from dietary fat, are not only important nutrients, but also act as signaling molecules and stimulate key biological functions. Recent physiological and pharmacological studies have shown that several G-protein coupled receptors, such as FFAR1–4, are receptors for FFAs. FFAR1 and FFAR4 are activated by medium- and long-chain fatty acids, whereas FFAR2 and FFAR3 are activated by short-chain fatty acids (SCFAs). These FFA receptors (FFARs) mediate various physiological functions, depending on the carbon chain length of the FFAs and the ligand specificity of the FFARs. Functional analyses have revealed that FFARs mediate important metabolic functions, such as peptide hormone secretion and inflammation, and thereby contribute to energy homeostasis. Since imbalances in energy homeostasis lead to metabolic disorders, such as obesity and T2D, FFARs are considered to be key therapeutic targets in these diseases. In particular, recent studies have shown that the administration of selective agonists of FFAR1 and FFAR4 improved glucose metabolism and ameliorated systemic metabolic disorders. Furthermore, the biological functions of SCFAs in anti-inflammation and energy metabolism are linked with the activation of FFAR2 and FFAR3. Hence, in this review, we summarize the physiological functions of FFARs and discuss the potential of selective ligands of FFARs for development as drugs to treat metabolic disorders, such as T2D and obesity.

This article reviews different glycemic parameters and is aimed to clarify the most dependable glycemic parameter that predicts renal preservation. Glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) are the most commonly ordered tests for the diagnosis of diabetes and are also used to indicate prevention of microvascular complications associated with diabetes. Some experts have concluded that HbA1c remains the only test that can predict microvascular complications but HbA1c is misleading with anemia. Other experts have reported that elevation of 2 hour postprandial glucose (2hPPG) or postprandial hyperglycemia is critical for the development of diabetic complications Measurement of parameters under fasting conditions is convenient in both clinical and research settings and are used to establish clinical guidelines for diabetes management and for rating efficacy of management. Despite the use of these diagnostic markers and a plethora of oral antidiabetic agents to treat diabetes, diabetic complications namely; cardiovascular disorders (CVD), end stage renal disease (ESRD) and amputation are on the rise. Although affirmative data on many of the complications are not available, the United States Renal Data System on ESRD is a testimonial to poor diabetes care. We have innovated dglucose (2hPPG-FBG) and found that dglucose relates significantly to renal function change measured by serum creatinine levels or estimated glomerular filtration rate. Our current study on dglucose confirms our previous finding and validates the importance of dglucose to aid in the management of diabetes and prevents diabetic complications. In conclusion, the new finding in this study is dglucose (2h-postprandial glucose-Fasting glucose) which convincingly relates to renal function changes. Since dglucose is a product of 2hPP glucose, keeping 2hPPG under tight control with intensive insulin therapy is fundamentally important. Further blood pressure control avoiding the use of renin-angiotensin inhibitor therapy is additive to renal protection in diabetes.

This study examined the factors associated with follow-up non-attendance (FUNA) and mortality among the adult patients with type 2 diabetes mellitus (T2DM). Data on 57780 T2DM patients from the 2009 diabetes registry were analyzed using multinomial logistic mixed model. Out of 57780 patients, 3140 (5.4%) were lost to follow-up and 203 (0.4%) patients had died. Compared with patients who were under active follow-up, men (OR 1.37), neither on insulin (OR 1.72), nor on antiplatelet agents (OR 1.47), having higher HbA1c (OR 1.15), higher LDL-C (OR 1.18) and complications (OR 1.33) were associated with FUNA. Older age (OR 1.09) and higher LDL-C (OR 2.27) have higher mortality. Across the four different health facilities, medication use (insulin and anti-platelet agents) to achieve better disease control in the younger age when diabetes complication is absent would not cause FUNA and might reduce mortality.