In this issue

A review of common infections in diabetes and the value of glycaemic control

Diabetes is associated with in vitro defects in innate and adaptive immunity, but their clinical relevance is unclear. Infections of skin, nails, mucous membranes, and feet are common and challenging. Diabetes is also a risk factor for serious respiratory infections, genitourinary infections and periodontal disease. Nosocomial, especially wound, infections are more likely to develop in diabetic inpatients, and intensive insulin therapy improves associated morbidity and mortality. This review concludes that there is a need for well-designed studies assessing the value of strict glycaemic control on outcome in other infections complicating diabetes.

Small, dense low-density-lipoproteins and the metabolic syndrome: A review

Small, dense low-density-lipoproteins (LDL) are associated with increased risk for cardiovascular diseases and diabetes mellitus. A reduction in LDL size has been reported in patients with coronary and non-coronary forms of atherosclerosis. LDL size has been accepted as an important predictor of cardiovascular events and progression of coronary artery disease as well as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Small, dense LDL, with elevated triglyceride levels and low HDL-cholesterol concentrations, constitute the ‘atherogenic lipoprotein phenotype’ that is a feature of type 2 diabetes and the metabolic syndrome. LDL size and subclasses show specific alterations in patients with the metabolic syndrome that probably significantly increase their cardiovascular risk; however, so far it has not been recommended to incorporate LDL size measurements into hypolipidemic treatment plans. Patients with type 2 diabetes are at high cardiovascular risk and there is still a question as to whether there are distinct groups with different cardiovascular risks and hence with different treatment goals. Measurements beyond traditional lipids, such as measurements on the presence of small, dense LDL in patients with the metabolic syndrome, may help identify cardiovascular risk subgroups. It might be possible, in the future, to personalize hypolipidemic treatments if more than the traditional lipids are taken into account.

Single nucleotide polymorphisms in the promoter of the Apolipoprotein M gene confer susceptibility to type 2 diabetes in han chinese

Apolipoprotein M (ApoM) is a recently identified high-density lipoprotein-associated apolipoprotein. Several studies have indicated that apoM is an important factor involved in the metabolism of high-density lipoprotein and cholesterol efflux in macrophages. Dyslipidemia that correlates with insulin resistance is one of the key features in type 2 diabetes. These authors propose that ApoM may be a candidate gene involved in the pathogenesis of this disease. They provide evidence that SNP T-778C in the proximal promoter region of the ApoM gene is associated with the levels of plasma cholesterol, fasting plasma glucose, and heightened risk of development of type 2 diabetes among Han Chinese.

Electronegative low-density lipoprotein subfraction from type 2 diabetic subjects is proatherogenic and unrelated to glycemic control

The electronegative LDL from type 2 diabetes patients shall decrease apoB and oxidizability, and increase triglyceride, non-esterified fatty acids, apoE, apoC-III, PAF acetylhydrolase activity, and aggregability versus electropositive LDL. It also showed lower binding affinity to the LDL receptor and a 2–3-fold higher ability to release IL-8 and MCP-1 in endothelial cells. These results suggest that the high electronegative LDL proportion plasma could promote accelerated atherosclerosis in patients with type 2 diabetes through increased residence time in plasma and induction of inflammatory responses in artery wall cells.

Cholesterol oxides as biomarkers of oxidative stress in diabetes mellitus

This study evaluated the formation of cholesterol oxides as biomarkers of oxidative stress in subjects with impaired glucose tolerance and diabetes. Cholesterol oxidation products were determined in the following groups: people with type 1 diabetes, type 2 diabetes or impaired glucose tolerance, as well as both children and adults without diabetes. Total cholesterol oxides were elevated in both the groups with diabetes compared to age-matched subjects without diabetes (p < 0.05). In patients with type 2 diabetes, the oral hypoglycemic drugs associated with insulin decreased the amount of nitrotyrosine without changing the concentrations of glucose and glycated haemoglobin while statins decreased the levels of cholesterol oxide.

High prevalence of glucose intolerance in primary hyperparathyroidism and the sustained benefit of parathyroidectomy

In patients with primary hyperparathyroidism, 51% had glucose intolerance, two-thirds of whom had type 2 diabetes mellitus by OGTT. Successful parathyroidectomy significantly reduced fasting and 2 hour plasma glucose. These beneficial effects persisted. This study highlights the benefit of OGTT to identify glucose intolerance in primary hyperparathyroidism and may provide a further indication for surgery in such patients.

Controlling Glucose in the ICU

Improvement in patient outcome with improved control of plasma glucose using IV insulin has been demonstrated in both surgical and medical critical care units. However, achieving such control consistently, across institutions, with economical use of resources and with the avoidance of hypoglycemia, has been challenging. Balkin et al present a protocol that employs a matrix to allow complex adjustments in insulin flow rate to be made without the need for correction factors or the use of multiplication. Its practicality and low incidence of associated hypoglycemia has allowed it be successfully employed at multiple institutions.

The benefits of early intervention in obese diabetic patients with FBCx—a new dietary fibre

Dietary fibre has been reported to reduce the absorption of dietary fat, prevent weight gain, and reduce blood lipid levels. In this double-blind study, the effects of a new dietary fibre, FBCx were tested in obese patients with type 2 diabetes over 3 months. The participants were instructed to take two 1-g tablets per fat-containing meal and not to change their eating patterns or daily routine. Dietary records showed that some participants changed their eating patterns; therefore, body weight data were adjusted according to energy intake. As a group, in the 30 days leading into the study, all participants experienced an average weight gain of 1.0 ± 0.4 kg. While those in the placebo group continued to gain weight during the study, those in the FBCx group maintained their weight. Those in the FBCx group required more energy to maintain their body weight while those in the placebo group required less (p < 0.05). Participants with hypertriglyceridemia showed a reduction in total cholesterol with FBCx, while those on placebo had an increase. Adiponectin was increased in the FBCx but reduced in the placebo group. FBCx has thus shown promising benefits in weight maintenance, a reduction of blood lipids, and an increase in adiponectin levels. It can be easily incorporated into a diabetic management regimen.

C-peptide improves neuropathy in type 1 diabetic BB/Wor-rats

The therapeutic effects of C-peptide on established neuropathy in the BB/Wor-rat were tested. Rats treated with continuous C-peptide infusion showed significant improvements of nerve conduction velocity, sural nerve myelinated fiber number, size, axonal area, regenearation, and overall neuropathy score. Full substitution dose given once daily subcutaneously showed prevention of further deterioration of neuropathy, whereas one-third of full substitution dose of C-peptide given subcutaneously resulted in a slower progression of neuropathy. These data show that C-peptide is effective in the treatment of diabetic neuropathy and that maximal therapeutic effects are achieved by continuous subcutaneous administration.

HUVECs from newborns with a strong family history of diabetes show diminished ROS synthesis in the presence of high glucose concentrations

A family history of type 2 diabetes mellitus increases the probability of developing diabetes and endothelial dysfunction. One possible mechanism involves augmented synthesis of reactive oxygen species (ROS) synthesis. This study measured the synthesis of ROS in human umbilical vein endothelial cells (HUVECs) obtained from healthy newborns with (experimental) and without (control) a strong family history of type 2 DM. The cells were exposed to various glucose concentrations for 24 and 48 h periods, then cell proliferation, mitochondrial activity, and mitochondrial membrane potential were determined. Intracellular ROS synthesis was measured in the presence or absence of the mitochondrial uncoupler CCCP, cytochalasin B, or diphenyleneiodonium. As opposed to control HUVECs, we found that experimental HUVECs exposed to 30 mmol/L glucose showed a 50% decrease in cell proliferation, a 90% reduction in mitochondrial activity, and a statistically significant inhibition of ROS synthesis in the presence of CCCP or cytochalasin B; diphenyleneiodonium had no effect. The authors conclude that mitochondria and NAD(P)H-oxidase from HUVECs obtained from healthy newborns with a family history of diabetes have a diminished response to very high glucose concentrations.