Very-low-energy diet for type 2 diabetes: An underutilized therapy?

BackgroundCurrent approaches to the management of type 2 diabetes focus on the early initiation of novel pharmacologic therapies and bariatric surgery.ObjectiveThe purpose of this study was to revisit the use of intensive, outpatient, behavioral weight management programs for the management of type 2 diabetes.DesignProspective observational study of 66 patients with type 2 diabetes and BMI ≥ 32 kg/m² who enrolled in a program designed to produce 15% weight reduction over 12 weeks using total meal replacement and low- to moderate-intensity physical activity.ResultsPatients were 53 ± 7 years of age (mean ± SD) and 53% were men. After 12 weeks, BMI fell from 40.1 ± 6.6 to 35.1 ± 6.5 kg/m². HbA1c fell from 7.4% ± 1.3% to 6.5% ± 1.2% (57.4 ± 12.3 to 47.7 ± 12.9 mmol/mol) in patients with established diabetes: 76% of patients with established diabetes and 100% of patients with newly diagnosed diabetes achieved HbA1c < 7.0% (53.0 mmol/mol). Improvement in HbA1c over 12 weeks was associated with higher baseline HbA1c and greater reduction in BMI.ConclusionsAn intensive, outpatient, behavioral weight management program significantly improved HbA1c in patients with type 2 diabetes over 12 weeks. The use of such programs should be encouraged among obese patients with type 2 diabetes.     

Management of type 2 diabetes mellitus: is it time for a paradigm shift?

Type 2 diabetes mellitus is a multi-organ disease that results from the combination of insulin resistance and a beta-cell secretory defect. The worldwide prevalence of type 2 diabetes has increased substantially during the past decade, and patients with this disease continue to experience a high incidence of morbidity and mortality. Because the complications associated with this disease affect multiple organ systems and have a dramatic impact on daily life, the importance of lowering glycosylated hemoglobin (HbA(1c)) levels to within the normal range cannot be overemphasized. The introduction in the past decade of several new classes of pharmacological agents to treat patients with type 2 diabetes now provides the opportunity to focus therapy on treating the underlying disease process instead of just reacting to the blood glucose levels. The thiazolidinediones are unique in their ability to modulate free fatty acid metabolism and to improve insulin sensitivity. These agents also exert numerous nonglycemic effects on the vasculature and lipid metabolism and may improve many of the risk factors associated with metabolic syndrome. Data from the United Kingdom Prospective Diabetes Study (UKPDS) group showed that conventional methods of managing type 2 diabetes, including the use of sulfonylureas or biguanides, do not provide long-term glycemic control. Consequently, new treatment paradigms stressing the earlier use of thiazolidinediones, either alone or in combination with metformin, may lead to more durable glycemic control, thus facilitating the reduction of complications in patients with type 2 diabetes.     

Glucolipotoxicity and beta cells in type 2 diabetes mellitus: target for durable therapy?

Type 2 diabetes mellitus (T2DM) is characterised by beta-cell failure in the setting of obesity-related insulin resistance. Progressive beta-cell dysfunction determines the course of the disease, regardless of the treatment used. There is mounting evidence that chronically elevated circulating levels of glucose and fatty acids contribute to relentless beta-cell function decline, by endorsing processes commonly referred to as glucolipotoxicity. Mechanisms related to glucolipotoxicity include endoplasmic reticulum (ER) stress, oxidative stress, mitochondrial dysfunction and islet inflammation. The most commonly prescribed blood-glucose lowering agents, metformin and sul-fonylurea, may temporarily improve glycaemic control, however, these drugs do not alter the continuous decline in beta-cell function in T2DM patients. Evidence exists that novel classes of drugs, the thiazolidinediones (TZDs) and incretin-based therapies, may be able to preserve beta-cell function and functional beta-cell mass, amongst others by reducing glucolipotoxicity in the beta cell. The durability of the effects of TZDs and incretin-based therapies on beta-cell function, whether given as monotherapy or combined with other treatment, should be addressed in future, long-term clinical studies.     

Hepatogenous diabetes: Is it time to separate it from type 2 diabetes?

By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent “toxic” effect on pancreatic islets resulting in β‐cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A_1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.     

Regulatory T cell dysfunction in type 1 diabetes: what’s broken and how can we fix it?

Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4⁺ and CD8⁺ T cells with specificity for islet autoantigens. In health, these potentially pathogenic T cells are held in check by multiple regulatory mechanisms, known collectively as ‘immunological tolerance’. This raises the question as to whether type 1 diabetes develops, at least in part, as a result of a defect in one or more of these control mechanisms. Immunological tolerance includes both central mechanisms (purging of the T cell repertoire of high-affinity autoreactive T cells in the thymus) and peripheral mechanisms, a major component of which is the action of a specialised subpopulation of T cells, known as regulatory T cells (Tregs). In this review, we highlight the evidence suggesting that a reduction in the functional capacity of different Treg populations contributes to disease development in type 1 diabetes. We also address current controversies regarding the putative causes of this defect and discuss strategies to correct it as a means to reduce or prevent islet destruction in a clinical setting.     

Is there a role for immune and anti-in-flammatory therapy in type 2 diabetes?

There is a growing body of evidence to suggest that type 2 diabetes is associated with a generalised activation of the innate immune system, in which there is a chronic low-grade inflammation. Further evidence for roles of inflammation in type 2 diabetes comes from clinical studies using either anti-inflammatory approaches or biological agents that target specific proinflammatory cytokine pathways to improve parameters of glucose control especially with IL-1β (Interleukin 1 β) antagonism and salsalate (non-acetylated prodrug of salicylate) treatment. In this review, recent evidence implicating the pathological involvement of the immune system in type 2 diabetes is examined, together with the role of potential treatment modalities targeting the immune system in the management of type 2 diabetes.     

Pathophysiological background for incretin therapy: is it capable of more than we think?

Incretin-based therapy functions through the increase of endogenous glucagon-like peptide-1 (GLP-1) levels due to inhibition of dipeptidyl peptidase-4--an enzyme degrading GLP-1 (gliptins) or through the administration of drugs activating GLP-1 receptor (GLP-1 agonists). Both approaches increase insulin and decrease glucagon secretion leading to improved diabetes compensation. The advantages of gliptins include little side effects, body weight neutrality and potential protective effects on pancreatic beta cells. GLP-1 agonists on the top of that consistently decrease body weight and blood pressure and their effects on diabetes compensation and likelihood of protective effects on beta cells is somewhat higher than those of gliptins. Another advantage of both approaches includes their safety with respect to induction of hypoglycemia. In addition to well-known metabolic effects, other potentially benefitial consequences of incretin based therapy in both type 2 diabetic and non-diabetic patients are anticipated. Direct positive effects of incretin-based therapy on myocardial metabolism and function as well as its positive influence on endothelial dysfunction and neuroprotective effects are intensively studied. The possible indications for GLP-1 agonists could be in future further widened to obese patients with type 1 diabetes and obese patients without diabetes. The aim of this review is to summarize both metabolic and extrapancreatic effects of incretin-based therapies and to outline perspectives of potential wider use of this treatment approach.     

Vitamin D and type 2 diabetes mellitus: where do we stand?

Aims

In-vitro and observational studies have established a link between vitamin D deficiency and different type 2 diabetes outcomes (insulin resistance, insulin secretion, glucose intolerance). Although the number of randomized controlled trials vs placebo is small, vitamin D (VTD) has been shown to prevent increases in glucose concentration and insulin resistance, enhance insulin sensitivity and reduce systolic blood pressure in type 2 diabetic patients.

Methods

In this review, we have focused on the potential mechanisms that might explain the association between VTD and type 2 diabetes mellitus (T2DM). We have also evaluated the different epidemiological and observational studies on the topic, as well as the various interventional studies.

Results

Although the in vitro studies appear to be promising in explaining the link between VTD metabolism and T2DM, the results of in vivo studies are conflicting. This could be related to differences in their methodological approaches.

Conclusion

Although more studies are needed to confirm the role of VTD in the treatment of T2DM, there is nevertheless enough evidence at this time to suggest a need to maintain 25-OH vitamin D levels in T2DM patients around 30 ng/mL over the course of a year.     

The benefit of aspirin therapy in type 2 diabetes: what is the evidence?

Many clinical guidelines recommend aspirin therapy for the prevention of cardiovascular events in individuals with type 2 diabetes. However it is unclear whether the level of evidence in guidelines is derived from studies carried out among individuals with diabetes. Medline and Embase databases were searched to retrieve studies published since 1990, evaluating the effect of aspirin on cardiovascular outcomes in subjects with type 2 diabetes. Four studies corresponded to the inclusion criteria. The three clinical trials retrieved could not prove from a statistical point of view, the benefits of aspirin therapy for subjects with type 2 diabetes. Reduction in cardiac mortality was found only in one observational study. Consequently, these findings suggest that the clinical guidelines have based their recommendations upon the expected benefit previously observed in other high-risk populations. Given the lack of hard evidence and the different well-known platelet physiology encountered in patients with diabetes, use of aspirin as a standard treatment at the highest level of evidence in guidelines for subjects with type 2 diabetes should be revisited.     

Neoadjuvant therapy for esophageal cancer--what can we accept?

BACKGROUND/AIMS: We evaluated neoadjuvant use in managing patients with esophageal carcinoma and its effects on the surgical resection and outcomes. METHODOLOGY: Patients prior to esophageal resection were offered the opportunity to receive a neoadjuvant cytostatic regimen (CDDP + FU, CDDP, or TAX + FU). Retrospective tumor chemoresistance analysis using the MTT test was also performed. RESULTS: Seventy patients were operated from 2001 until May 2004. A total of 55 resections were performed with preoperative neoadjuvant therapy and 15 elected to only undergo surgery without neoadjuvant therapy. No deaths occurred as a result of surgery or neoadjuvant therapy, but complications included fistulas and hemorrhages. CONCLUSIONS: There was no significant difference between the postoperative complications among the neoadjuvant and non-neoadjuvant groups. This therapy therefore does not have any influence on the course or results of surgical resection. MTT testing did not demonstrate any particular usefulness in tailoring neoadjuvant therapy. Chemoresistance could only be retrospectively evaluated and the results may be affected after cytostatic therapy. The long-term outcomes have not been evaluated yet due to the short follow-up time in our patient group.