Does "afternoon diabetes" predict diabetes?

Twenty-eight men were given morning and afternoon oral glucose tolerance tests in 1969 and again in 1975. According to British Diabetic Association criteria all 28 had normal morning values in 1969 but seven had "afternoon diabetes". Four men had diabetic values in the morning in 1975 but only two of these had had afternoon diabetes in 1969. Better prediction of subsequent diabetes was obtained by calculating the area under the morning glucose tolerance curve in 1969. All four men who progressed to diabetes had areas exceeding 1000 units, which distinguished them absolutely from the other 24. They also tended to be more obese, but this was less predictive of subsequent diabetes.     

Curing diabetes with transplantation?

Type 1 diabetes affects >1 million people in the United States, where it accounts for up to 10% of all diabetes cases. Glycemic control via the use of exogenous insulin injections in diabetic patients is incomplete, resulting in multiple long-term complications such as retinopathy, neuropathy, vasculopathy, and nephropathy. The goal of beta-cell replacement by whole-pancreas or islet transplantation is to achieve long-term insulin independence, and the proposed benefits are improved quality of life, prevention of recurrent diabetic nephropathy, stabilization or improvement in secondary complications, and improved mortality. No other regimen of insulin delivery can achieve this level of physiologic regulation.     

Epidemiology of diabetes mellitus in children in Hong Kong-the Hong Kong childhood diabetes register

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Oral hypoglycemic agents for gestational diabetes mellitus?

INTRODUCTION: Gestational diabetes mellitus (GDM), the most frequent medical complication of pregnancy, is associated with several adverse outcomes over the short- and long-term for both mother and offspring. Standard treatment for GDM consists of insulin injections. Oral hypoglycemic agents (OHAs), on the other hand, are still the subject of controversy. Although OHAs are seemingly as efficient as insulin and may provide better quality of life, congenital malformations and unknown long-term effects are still feared. AREAS COVERED: Recent data on the pharmacokinetics of two OHAs (glyburide and metformin) and their clinical use for GDM are reviewed, with a focus on clinical trials and observational studies comparing insulin with glyburide or metformin (1960 - 2010). The review will provide a comprehensive overview of the pros and cons of OHA usage, an appreciation of OHAs' efficiency for the purpose of controlling glycemia and embryogenetic basics relating to congenital malformations. EXPERT OPINION: While insulin treatment is an effective therapy for controlling maternal glycemia, it nevertheless requires sufficient education and skills on the part of the patient to manage properly and may cause hypoglycemia, fear and anxiety. Oral treatment as a more user-friendly alternative may thus facilitate the control of GDM in some patients.     

Viral infection--a cure for type 1 diabetes?

Autoimmune diseases are thought to arise as a detrimental combination of genetic predisposition and environmental factors. Because of their potential for direct cellular damage and causing extensive inflammation, viruses are one of the major candidates for triggering autoimmunity. Although there is epidemiological evidence, direct proof for viruses as causative agents for autoimmune disease is hard to get since most viruses have been eliminated from the system by the time of diagnosis. However, evidence from various animal models suggests that viruses can indeed initiate or accelerate autoimmune diseases, such as type 1 diabetes or experimental allergic encephalomyelitis. In contrast, viruses have been also demonstrated to abrogate autoimmune disease in animal models. These observations might offer one explanation why increased frequencies of allergies and autoimmune diseases parallel with higher hygienic standards. This review reflects on the epidemiological evidence for the association of viruses with autoimmune diseases, the experimental evidence for viruses to abrogate an ongoing autoimmune destruction and evaluates the possibility for a therapeutic application.     

Inhibition of cytokine-induced β cell apoptosis via laccase and its therapeutic advantages for insulin-dependent diabetes mellitus, type 1 diabetes

In pancreatic islets, free radical formation produced upon exposure to proinflammatory cytokines mediates β cell destruction, which ultimately leads to type 1 diabetes (T1D). In this study, we examined whether laccase, a family of the blue copper protein, can be successfully used to prevent β cells from cytokine-mediated apoptosis. Non-obese diabetic (NOD) mice were used for these experiments. In parallel, the RINm5f β cell line was employed as a model system for in vitro experiments. The results demonstrated that laccase effectively scavenged peroxinitrite, which can be formed by nitric oxide, and upregulated the expression of antioxidant enzymes, such as manganese superoxide dismutase (MnSOD) and catalase. Interestingly, laccase balanced pro- (Bax) and anti-apoptotic (Bcl-2) proteins in terms of both the mRNA and protein levels with a downregulation of cytochrome c protein in RINm5f cells. In addition, laccase maintained blood glucose concentrations at a normal level with a simultaneous increase in plasma insulin levels during the spontaneous induction of diabetes in NOD mice. In conclusion, the antioxidant potentials of laccase in scavenging free radicals and upregulation of antioxidant enzymes may exert its pro-survival effect by counteracting the increased intracellular oxidative stress, and, consequently, by inhibiting apoptosis induced by cytokine-mediated activation during the course of T1D.     

Pharmacotherapy of ‘treatment resistant’ type 2 diabetes

Introduction: Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice.

Areas covered: This article proposes a definition for ‘treatment resistant diabetes’, analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies.

Expert opinion: Before considering intensifying the pharmacotherapy of a patient with poorly controlled T2D, it is important to verify treatment adherence, target obesity and consider various non pharmacological improvement quality interventions. If treatment resistant diabetes is defined as not achieving glycated haemoglobin target despite oral triple therapy with a third glucose-lowering agent added to metformin-sulfonylurea dual treatment, the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a sodium glucose cotransporter type 2 (SGLT2) inhibitor may offer new opportunities before considering injectable therapies. Insulin basal therapy (± metformin) may be optimized by the addition of a SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist.     

Bariatric surgery or medicine for type 2 diabetes?

Diet and medical treatment are the standard treatment for type 2 diabetes. In obese subjects with type 2 diabetes, bariatric surgery is effective in resolving diabetes. Two clinical trials comparing bariatric surgery to medical treatment were evaluated. Both the Surgical Treatment And Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial (laparoscopic Roux-En Y gastric bypass and sleeve gastrectomy) and the DIet and medical therapy versus BAriatric SurgerY in type 2 diabetes (DIBASY) trial (laparoscopic gastric bypass and biliopancreatic-diversion) showed that surgery was more effective than medical care in resolving or managing type 2 diabetes. Larger studies, or a compilation of studies, are needed to determine whether one of these procedures is better, or if they are all similarly effective, and this should also be weighed against the risk of the operations.     

Ruboxistaurin: PKC-β inhibition for complications of diabetes

Diabetes mellitus is the most common cause of blindness among working-age adults, with a prevalence of 7 – 8% of adults in the USA, and is one of the most common causes of renal failure requiring kidney transplant and the most common cause of non-traumatic lower limb amputation in developed nations . The role of the intracellular signaling enzyme protein kinase C (PKC) in the development of diabetic complications has become a field of intense research interest. An inhibitor of the PKC-β isoform ruboxistaurin (RBX) has in vitro and in vivo benefits in ameliorating disturbances of cell regulation and blood flow related to hyperglycemia. The benefit of RBX for peripheral neuropathy has not been successfully demonstrated in Phase III trials. Although there was a beneficial effect of RBX on nephropathy in a pilot study, there has been no further clinical development for this indication. The major cause of visual disability – diabetic macular edema – seems to respond to RBX treatment with both anatomic and functional benefits. The manufacturer, Eli Lilly Co., has received an approvable letter from the FDA for the prevention of vision loss in patients with diabetic retinopathy with RBX, pending results of additional clinical trials for this indication.     

Is Ramipril the pril for diabetes and kidney disease?

Ramipril is safe and effective in the treatment of hypertension and heart failure, but this is not reviewed here. Ramipril is a lipophilic angiotensin-converting enzyme inhibitor suitable for once-daily administration. In addition to decreasing angiotensin II and increasing bradykinin levels, ramipril increases the levels of vasodilatory renal medullary neutral lipids and inhibits platelet-derived growth factor-induced proliferation of glomerulus cells. Ramipril also decreases transforming growth factor-beta in the kidney. Changes in kidney structure and proteinuria are characteristics of the streptozotocin (STZ) rat model of diabetes, and these are prevented by ramipril. In STZ diabetes, doses of ramipril that have no effect on blood pressure reverse vascular hypertrophy. In animal models of kidney failure (subtotal nephrectomy, stroke-prone spontaneously hypertensive rats), ramipril is renoprotective and some of this renoprotective effect is independent of blood pressure lowering. In humans, clinical doses of ramipril probably do not modify glucose metabolism but do reduce the levels of LDL- and HDL-cholesterol. In clinical trials of renal effects, ramipril has been shown to increase cortical nephron flow in hypertension and to reduce proteinuria in patients with and without diabetes and/or hypertension. Some of the smaller clinical trials showed beneficial effects on kidney function with low doses of ramipril that do not lower blood pressure. A large clinical trial in nondiabetic proteinuria, the Ramipril Efficacy in Nephropathy (REIN) trial, has shown that ramipril 1.25 mg/day, which does not lower blood pressure, arrested the decline in glomerular filtration rate and prolonged the time to end-stage renal failure. In diabetic patients who have had a previous cardiovascular event or having one other cardiovascular risk factor, the MICRO-HOPE clinical trial showed that ramipril lowers the combined risk of myocardial infarction, stroke and cardiovascular death by 25%. In conclusion, ramipril has proven beneficial effects in kidney disease alone or in association with diabetes and in diabetes without kidney disease, and is the pril for diabetes and kidney disease. (c) 2001 Prous Science. All rights reserved.     

Is exenatide advancing the treatment of type 2 diabetes?

Glucagon-like peptide 1 is an intestinal peptide hormone that is secreted in response to food to regulate the postprandial blood glucose concentration. Exendin-4 is a 39-amino acid peptide that acts as an agonist at the glucagon-like peptide 1 receptor. Synthetic exendin-4 (exenatide) has recently been trialled in patients with Type 2 diabetes taking either metformin alone or a combination of metformin and a sulfonylurea. In both trials, exenatide 5 and 10 microg s.c. was shown to improve glycaemic control, with few adverse events. Exenatide represents a new and useful addition to the medicines used to treat Type 2 diabetes.     

Can thiazolidinediones delay disease progression in type 2 diabetes?

BACKGROUND: Type 2 diabetes results from increasing insulin resistance coupled with progressive loss of beta-cell function. Further deterioration of beta-cell function is associated with progression of diabetes and the potential development of microvascular and macrovascular complications. SCOPE: This review examines current knowledge of beta-cell function and uses this information to assess how the results of ongoing trials could increase our understanding of disease progression and potential interventions. Data were derived from a Medline search using the search terms 'beta-cell dysfunction', 'IGT', 'thiazolidinediones', 'metformin', and 'sulfonylurea'. RESULTS: The mechanisms that underlie beta-cell dysfunction are complex and most likely involve the interplay of a range of factors that reduce both beta-cell mass and secretory function. These include detrimental effects associated with hyperglycemia itself, elevated free fatty acids, and inflammatory responses linked to adipocyte-derived cytokines, with apoptosis a key underlying mechanism. Early intervention with treatments that address these defects, and preserve beta-cell function while improving insulin sensitivity, may delay disease progression in patients with type 2 diabetes and also prevent the development of diabetes in 'at-risk' individuals. Two of the studies examining the effects of interventions on development and progression of diabetes that are due to report shortly are ADOPT (A Diabetes Outcome Progression Trial), comparing a thiazolidinedione, metformin and a sulfonylurea in patients with type 2 diabetes not previously treated with oral hypoglycemic agents, and DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication), assessing the effects of a thiazolidinedione and an angiotensin-converting enzyme inhibitor in subjects with impaired glucose tolerance and/or impaired fasting glucose. CONCLUSIONS: Although we do not have a full understanding of the mechanisms driving progression of type 2 diabetes, there is growing evidence that we may be able to modulate them and thereby improve patient outcomes.